JP6216321B2 - 二重特異性抗体の構築の改善 - Google Patents
二重特異性抗体の構築の改善 Download PDFInfo
- Publication number
- JP6216321B2 JP6216321B2 JP2014535885A JP2014535885A JP6216321B2 JP 6216321 B2 JP6216321 B2 JP 6216321B2 JP 2014535885 A JP2014535885 A JP 2014535885A JP 2014535885 A JP2014535885 A JP 2014535885A JP 6216321 B2 JP6216321 B2 JP 6216321B2
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- domain
- antibodies
- hinge
- half antibody
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000010276 construction Methods 0.000 title description 64
- 230000001976 improved effect Effects 0.000 title description 9
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 287
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 283
- 229920001184 polypeptide Polymers 0.000 claims description 275
- 108090000623 proteins and genes Proteins 0.000 claims description 227
- 102000004169 proteins and genes Human genes 0.000 claims description 205
- 238000000034 method Methods 0.000 claims description 173
- 210000004027 cell Anatomy 0.000 claims description 158
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims description 131
- 239000004475 Arginine Substances 0.000 claims description 85
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 84
- 239000000203 mixture Substances 0.000 claims description 83
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 76
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 75
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 74
- 229960003180 glutathione Drugs 0.000 claims description 64
- 239000002904 solvent Substances 0.000 claims description 61
- 241000588724 Escherichia coli Species 0.000 claims description 47
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 44
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 44
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 44
- 238000004519 manufacturing process Methods 0.000 claims description 36
- 108010024636 Glutathione Proteins 0.000 claims description 35
- 238000000746 purification Methods 0.000 claims description 35
- 239000003381 stabilizer Substances 0.000 claims description 34
- 230000001603 reducing effect Effects 0.000 claims description 33
- 238000002156 mixing Methods 0.000 claims description 30
- 230000001580 bacterial effect Effects 0.000 claims description 20
- 210000004962 mammalian cell Anatomy 0.000 claims description 17
- 238000006467 substitution reaction Methods 0.000 claims description 16
- 150000001483 arginine derivatives Chemical class 0.000 claims description 11
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 10
- 230000003647 oxidation Effects 0.000 claims description 10
- 238000007254 oxidation reaction Methods 0.000 claims description 10
- 210000004899 c-terminal region Anatomy 0.000 claims description 9
- 241000701447 unidentified baculovirus Species 0.000 claims description 8
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 7
- 238000011534 incubation Methods 0.000 claims description 6
- 150000002410 histidine derivatives Chemical class 0.000 claims description 5
- 150000002411 histidines Chemical class 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 210000005253 yeast cell Anatomy 0.000 claims description 5
- 229930006000 Sucrose Natural products 0.000 claims description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 4
- 239000005720 sucrose Substances 0.000 claims description 4
- 238000006471 dimerization reaction Methods 0.000 claims description 3
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 claims description 3
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 description 188
- 229960003121 arginine Drugs 0.000 description 77
- 235000009697 arginine Nutrition 0.000 description 76
- 230000027455 binding Effects 0.000 description 71
- 229960002885 histidine Drugs 0.000 description 68
- 235000014304 histidine Nutrition 0.000 description 66
- 239000000427 antigen Substances 0.000 description 59
- 108091007433 antigens Proteins 0.000 description 57
- 102000036639 antigens Human genes 0.000 description 57
- 239000003638 chemical reducing agent Substances 0.000 description 43
- 239000000543 intermediate Substances 0.000 description 38
- 102100040247 Tumor necrosis factor Human genes 0.000 description 37
- 230000002776 aggregation Effects 0.000 description 37
- 238000004220 aggregation Methods 0.000 description 36
- 239000013598 vector Substances 0.000 description 36
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 35
- 125000003275 alpha amino acid group Chemical group 0.000 description 35
- 125000000539 amino acid group Chemical group 0.000 description 35
- 230000015572 biosynthetic process Effects 0.000 description 32
- 239000012634 fragment Substances 0.000 description 31
- 235000001014 amino acid Nutrition 0.000 description 30
- 230000014509 gene expression Effects 0.000 description 26
- 102000039446 nucleic acids Human genes 0.000 description 26
- 108020004707 nucleic acids Proteins 0.000 description 26
- 150000007523 nucleic acids Chemical class 0.000 description 26
- 229940024606 amino acid Drugs 0.000 description 24
- 108060003951 Immunoglobulin Proteins 0.000 description 23
- 150000001413 amino acids Chemical class 0.000 description 23
- 102000018358 immunoglobulin Human genes 0.000 description 23
- 238000001556 precipitation Methods 0.000 description 23
- 239000002609 medium Substances 0.000 description 21
- 238000010438 heat treatment Methods 0.000 description 20
- 230000001965 increasing effect Effects 0.000 description 19
- 239000000243 solution Substances 0.000 description 19
- 108090000176 Interleukin-13 Proteins 0.000 description 18
- 102000003816 Interleukin-13 Human genes 0.000 description 18
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
- 230000002829 reductive effect Effects 0.000 description 18
- 108010076504 Protein Sorting Signals Proteins 0.000 description 17
- 238000005734 heterodimerization reaction Methods 0.000 description 17
- 108020004414 DNA Proteins 0.000 description 16
- 230000000694 effects Effects 0.000 description 16
- 230000003993 interaction Effects 0.000 description 16
- 239000012636 effector Substances 0.000 description 15
- 239000013604 expression vector Substances 0.000 description 15
- 230000006870 function Effects 0.000 description 15
- 238000003776 cleavage reaction Methods 0.000 description 14
- -1 genenase Proteins 0.000 description 14
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 13
- 230000009467 reduction Effects 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- 230000007017 scission Effects 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 11
- 235000018417 cysteine Nutrition 0.000 description 11
- 238000010979 pH adjustment Methods 0.000 description 11
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 10
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 10
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 10
- 229930064664 L-arginine Natural products 0.000 description 10
- 235000014852 L-arginine Nutrition 0.000 description 10
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 10
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 10
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 10
- 238000004113 cell culture Methods 0.000 description 10
- 238000005516 engineering process Methods 0.000 description 10
- 230000014759 maintenance of location Effects 0.000 description 10
- 230000035772 mutation Effects 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 9
- 102000035195 Peptidases Human genes 0.000 description 9
- 108091005804 Peptidases Proteins 0.000 description 9
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 9
- 229960002433 cysteine Drugs 0.000 description 9
- 239000013628 high molecular weight specie Substances 0.000 description 9
- 230000002209 hydrophobic effect Effects 0.000 description 9
- 230000008676 import Effects 0.000 description 9
- 230000010076 replication Effects 0.000 description 9
- 238000001542 size-exclusion chromatography Methods 0.000 description 9
- 238000013518 transcription Methods 0.000 description 9
- 230000035897 transcription Effects 0.000 description 9
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 8
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 8
- 239000004365 Protease Substances 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 108020001096 dihydrofolate reductase Proteins 0.000 description 8
- 239000003623 enhancer Substances 0.000 description 8
- 229940088598 enzyme Drugs 0.000 description 8
- 229960004198 guanidine Drugs 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- QZNNVYOVQUKYSC-JEDNCBNOSA-N (2s)-2-amino-3-(1h-imidazol-5-yl)propanoic acid;hydron;chloride Chemical compound Cl.OC(=O)[C@@H](N)CC1=CN=CN1 QZNNVYOVQUKYSC-JEDNCBNOSA-N 0.000 description 7
- 102100036302 C-C chemokine receptor type 6 Human genes 0.000 description 7
- 108010053070 Glutathione Disulfide Proteins 0.000 description 7
- 101000716068 Homo sapiens C-C chemokine receptor type 6 Proteins 0.000 description 7
- 108090000978 Interleukin-4 Proteins 0.000 description 7
- 102000004388 Interleukin-4 Human genes 0.000 description 7
- 229910019142 PO4 Inorganic materials 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000000356 contaminant Substances 0.000 description 7
- OOTFVKOQINZBBF-UHFFFAOYSA-N cystamine Chemical compound CCSSCCN OOTFVKOQINZBBF-UHFFFAOYSA-N 0.000 description 7
- 229940099500 cystamine Drugs 0.000 description 7
- 238000010494 dissociation reaction Methods 0.000 description 7
- 230000005593 dissociations Effects 0.000 description 7
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical group SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 7
- 238000000855 fermentation Methods 0.000 description 7
- 230000004151 fermentation Effects 0.000 description 7
- YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 description 7
- 239000003550 marker Substances 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 7
- 239000010452 phosphate Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000007790 solid phase Substances 0.000 description 7
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 6
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 6
- 102100036846 C-C motif chemokine 21 Human genes 0.000 description 6
- 102100036849 C-C motif chemokine 24 Human genes 0.000 description 6
- 102100021936 C-C motif chemokine 27 Human genes 0.000 description 6
- 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 6
- 102100025618 C-X-C chemokine receptor type 6 Human genes 0.000 description 6
- MFBYPDKTAJXHNI-VKHMYHEASA-N Gly-Cys Chemical compound [NH3+]CC(=O)N[C@@H](CS)C([O-])=O MFBYPDKTAJXHNI-VKHMYHEASA-N 0.000 description 6
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 6
- 101000713085 Homo sapiens C-C motif chemokine 21 Proteins 0.000 description 6
- 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 6
- 108010002616 Interleukin-5 Proteins 0.000 description 6
- 102100039897 Interleukin-5 Human genes 0.000 description 6
- 101001018085 Lysobacter enzymogenes Lysyl endopeptidase Proteins 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 101710120037 Toxin CcdB Proteins 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 239000007983 Tris buffer Substances 0.000 description 6
- 102100024584 Tumor necrosis factor ligand superfamily member 12 Human genes 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 6
- 229940072221 immunoglobulins Drugs 0.000 description 6
- 238000005342 ion exchange Methods 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 238000012423 maintenance Methods 0.000 description 6
- 229960003151 mercaptamine Drugs 0.000 description 6
- 210000001236 prokaryotic cell Anatomy 0.000 description 6
- 235000019419 proteases Nutrition 0.000 description 6
- 238000010188 recombinant method Methods 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 230000009870 specific binding Effects 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 6
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 5
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 5
- 102100032937 CD40 ligand Human genes 0.000 description 5
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 5
- 108010087819 Fc receptors Proteins 0.000 description 5
- 102000009109 Fc receptors Human genes 0.000 description 5
- 102100035233 Furin Human genes 0.000 description 5
- 108090001126 Furin Proteins 0.000 description 5
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 5
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 5
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 5
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 5
- 102000003810 Interleukin-18 Human genes 0.000 description 5
- 108090000171 Interleukin-18 Proteins 0.000 description 5
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 5
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 5
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 5
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 5
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 5
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 5
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 5
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 5
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 5
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 239000004202 carbamide Substances 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 229960003067 cystine Drugs 0.000 description 5
- 230000002950 deficient Effects 0.000 description 5
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 5
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 5
- 239000013613 expression plasmid Substances 0.000 description 5
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 5
- 239000000833 heterodimer Substances 0.000 description 5
- 230000016784 immunoglobulin production Effects 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 5
- 235000015097 nutrients Nutrition 0.000 description 5
- 238000003752 polymerase chain reaction Methods 0.000 description 5
- 108091033319 polynucleotide Proteins 0.000 description 5
- 102000040430 polynucleotide Human genes 0.000 description 5
- 239000002157 polynucleotide Substances 0.000 description 5
- 238000004007 reversed phase HPLC Methods 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 239000013589 supplement Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 239000011534 wash buffer Substances 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102100022718 Atypical chemokine receptor 2 Human genes 0.000 description 4
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 4
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 4
- 102100037853 C-C chemokine receptor type 4 Human genes 0.000 description 4
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 4
- 102100023702 C-C motif chemokine 13 Human genes 0.000 description 4
- 102100023700 C-C motif chemokine 16 Human genes 0.000 description 4
- 102100023701 C-C motif chemokine 18 Human genes 0.000 description 4
- 102100036848 C-C motif chemokine 20 Human genes 0.000 description 4
- 102100021933 C-C motif chemokine 25 Human genes 0.000 description 4
- 102100021935 C-C motif chemokine 26 Human genes 0.000 description 4
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 4
- 102100032366 C-C motif chemokine 7 Human genes 0.000 description 4
- 102100028989 C-X-C chemokine receptor type 2 Human genes 0.000 description 4
- 102100036150 C-X-C motif chemokine 5 Human genes 0.000 description 4
- 102100036153 C-X-C motif chemokine 6 Human genes 0.000 description 4
- 102100036170 C-X-C motif chemokine 9 Human genes 0.000 description 4
- 108010029697 CD40 Ligand Proteins 0.000 description 4
- 101150013553 CD40 gene Proteins 0.000 description 4
- 102100025221 CD70 antigen Human genes 0.000 description 4
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 4
- 229940045513 CTLA4 antagonist Drugs 0.000 description 4
- 102100039196 CX3C chemokine receptor 1 Human genes 0.000 description 4
- 108020004705 Codon Proteins 0.000 description 4
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 101000867232 Escherichia coli Heat-stable enterotoxin II Proteins 0.000 description 4
- 102100028417 Fibroblast growth factor 12 Human genes 0.000 description 4
- 102100028043 Fibroblast growth factor 3 Human genes 0.000 description 4
- 102100028072 Fibroblast growth factor 4 Human genes 0.000 description 4
- 102100028071 Fibroblast growth factor 7 Human genes 0.000 description 4
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 241000238631 Hexapoda Species 0.000 description 4
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 4
- 101000678892 Homo sapiens Atypical chemokine receptor 2 Proteins 0.000 description 4
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 4
- 101000716070 Homo sapiens C-C chemokine receptor type 9 Proteins 0.000 description 4
- 101000978375 Homo sapiens C-C motif chemokine 16 Proteins 0.000 description 4
- 101000978371 Homo sapiens C-C motif chemokine 18 Proteins 0.000 description 4
- 101000897480 Homo sapiens C-C motif chemokine 2 Proteins 0.000 description 4
- 101000713099 Homo sapiens C-C motif chemokine 20 Proteins 0.000 description 4
- 101000713078 Homo sapiens C-C motif chemokine 24 Proteins 0.000 description 4
- 101000897486 Homo sapiens C-C motif chemokine 25 Proteins 0.000 description 4
- 101000897494 Homo sapiens C-C motif chemokine 27 Proteins 0.000 description 4
- 101000916059 Homo sapiens C-X-C chemokine receptor type 2 Proteins 0.000 description 4
- 101000856683 Homo sapiens C-X-C chemokine receptor type 6 Proteins 0.000 description 4
- 101000947186 Homo sapiens C-X-C motif chemokine 5 Proteins 0.000 description 4
- 101000917234 Homo sapiens Fibroblast growth factor 12 Proteins 0.000 description 4
- 101001060280 Homo sapiens Fibroblast growth factor 3 Proteins 0.000 description 4
- 101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 0.000 description 4
- 101000843810 Homo sapiens Hydroxycarboxylic acid receptor 1 Proteins 0.000 description 4
- 101001076292 Homo sapiens Insulin-like growth factor II Proteins 0.000 description 4
- 101000998146 Homo sapiens Interleukin-17A Proteins 0.000 description 4
- 101001017968 Homo sapiens Leukotriene B4 receptor 1 Proteins 0.000 description 4
- 101000830598 Homo sapiens Tumor necrosis factor ligand superfamily member 12 Proteins 0.000 description 4
- 102100030642 Hydroxycarboxylic acid receptor 1 Human genes 0.000 description 4
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 4
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 4
- 102100025947 Insulin-like growth factor II Human genes 0.000 description 4
- 108010065805 Interleukin-12 Proteins 0.000 description 4
- 102000013462 Interleukin-12 Human genes 0.000 description 4
- 102100020791 Interleukin-13 receptor subunit alpha-1 Human genes 0.000 description 4
- 102100033461 Interleukin-17A Human genes 0.000 description 4
- 102100036678 Interleukin-27 subunit alpha Human genes 0.000 description 4
- 102100039064 Interleukin-3 Human genes 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- 108090001007 Interleukin-8 Proteins 0.000 description 4
- 102000004890 Interleukin-8 Human genes 0.000 description 4
- 108010002335 Interleukin-9 Proteins 0.000 description 4
- 102100026871 Interleukin-9 Human genes 0.000 description 4
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- 102000016267 Leptin Human genes 0.000 description 4
- 108010092277 Leptin Proteins 0.000 description 4
- 102100033374 Leukotriene B4 receptor 1 Human genes 0.000 description 4
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 108020004511 Recombinant DNA Proteins 0.000 description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 4
- 108010000499 Thromboplastin Proteins 0.000 description 4
- 102100030859 Tissue factor Human genes 0.000 description 4
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 4
- 102000012883 Tumor Necrosis Factor Ligand Superfamily Member 14 Human genes 0.000 description 4
- 108010065158 Tumor Necrosis Factor Ligand Superfamily Member 14 Proteins 0.000 description 4
- 102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 description 4
- 102100032100 Tumor necrosis factor ligand superfamily member 8 Human genes 0.000 description 4
- 102100032101 Tumor necrosis factor ligand superfamily member 9 Human genes 0.000 description 4
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 4
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 4
- 102100038232 Vascular endothelial growth factor C Human genes 0.000 description 4
- 229960000723 ampicillin Drugs 0.000 description 4
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 4
- 230000003321 amplification Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 229960003589 arginine hydrochloride Drugs 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
- 239000000539 dimer Substances 0.000 description 4
- 230000009881 electrostatic interaction Effects 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 230000002349 favourable effect Effects 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 108010037896 heparin-binding hemagglutinin Proteins 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 210000003292 kidney cell Anatomy 0.000 description 4
- 229940039781 leptin Drugs 0.000 description 4
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 4
- 239000012160 loading buffer Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 4
- SXTAYKAGBXMACB-UHFFFAOYSA-N methionine sulfoximine Chemical compound CS(=N)(=O)CCC(N)C(O)=O SXTAYKAGBXMACB-UHFFFAOYSA-N 0.000 description 4
- 238000003199 nucleic acid amplification method Methods 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 4
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 4
- 230000005030 transcription termination Effects 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- 238000011144 upstream manufacturing Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 3
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 3
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 3
- 208000002109 Argyria Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 3
- 102100023698 C-C motif chemokine 17 Human genes 0.000 description 3
- 102100036842 C-C motif chemokine 19 Human genes 0.000 description 3
- 102100036850 C-C motif chemokine 23 Human genes 0.000 description 3
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 3
- 102100025279 C-X-C motif chemokine 11 Human genes 0.000 description 3
- 102100039398 C-X-C motif chemokine 2 Human genes 0.000 description 3
- 102100036189 C-X-C motif chemokine 3 Human genes 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- 102000036364 Cullin Ring E3 Ligases Human genes 0.000 description 3
- 108091007045 Cullin Ring E3 Ligases Proteins 0.000 description 3
- 241000701022 Cytomegalovirus Species 0.000 description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 102000001301 EGF receptor Human genes 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 108010039471 Fas Ligand Protein Proteins 0.000 description 3
- 102100028413 Fibroblast growth factor 11 Human genes 0.000 description 3
- 102100035323 Fibroblast growth factor 18 Human genes 0.000 description 3
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 3
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 3
- 101000978362 Homo sapiens C-C motif chemokine 17 Proteins 0.000 description 3
- 101000713106 Homo sapiens C-C motif chemokine 19 Proteins 0.000 description 3
- 101000713081 Homo sapiens C-C motif chemokine 23 Proteins 0.000 description 3
- 101000889128 Homo sapiens C-X-C motif chemokine 2 Proteins 0.000 description 3
- 101000947193 Homo sapiens C-X-C motif chemokine 3 Proteins 0.000 description 3
- 101000917236 Homo sapiens Fibroblast growth factor 11 Proteins 0.000 description 3
- 101000878128 Homo sapiens Fibroblast growth factor 18 Proteins 0.000 description 3
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 3
- 101100232357 Homo sapiens IL13RA1 gene Proteins 0.000 description 3
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 3
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 3
- 101000764535 Homo sapiens Lymphotoxin-alpha Proteins 0.000 description 3
- 101001128431 Homo sapiens Myeloid-derived growth factor Proteins 0.000 description 3
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 3
- 102000026633 IL6 Human genes 0.000 description 3
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 3
- 102000003777 Interleukin-1 beta Human genes 0.000 description 3
- 108090000193 Interleukin-1 beta Proteins 0.000 description 3
- 102000003814 Interleukin-10 Human genes 0.000 description 3
- 108090000174 Interleukin-10 Proteins 0.000 description 3
- 102000003815 Interleukin-11 Human genes 0.000 description 3
- 108090000177 Interleukin-11 Proteins 0.000 description 3
- 108090000172 Interleukin-15 Proteins 0.000 description 3
- 102000003812 Interleukin-15 Human genes 0.000 description 3
- 101800003050 Interleukin-16 Proteins 0.000 description 3
- 102000049772 Interleukin-16 Human genes 0.000 description 3
- 102100039879 Interleukin-19 Human genes 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 102100020873 Interleukin-2 Human genes 0.000 description 3
- 102100037795 Interleukin-6 receptor subunit beta Human genes 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 3
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 description 3
- 239000006137 Luria-Bertani broth Substances 0.000 description 3
- 102100026238 Lymphotoxin-alpha Human genes 0.000 description 3
- 239000012515 MabSelect SuRe Substances 0.000 description 3
- 108090000157 Metallothionein Proteins 0.000 description 3
- 108010006519 Molecular Chaperones Proteins 0.000 description 3
- 102000005431 Molecular Chaperones Human genes 0.000 description 3
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 3
- 229930193140 Neomycin Natural products 0.000 description 3
- 241000589516 Pseudomonas Species 0.000 description 3
- 102000014128 RANK Ligand Human genes 0.000 description 3
- 108010025832 RANK Ligand Proteins 0.000 description 3
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 3
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
- 239000004473 Threonine Substances 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 101710187743 Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 3
- 102100033732 Tumor necrosis factor receptor superfamily member 1A Human genes 0.000 description 3
- 102100022205 Tumor necrosis factor receptor superfamily member 21 Human genes 0.000 description 3
- 238000005411 Van der Waals force Methods 0.000 description 3
- 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 description 3
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 238000001042 affinity chromatography Methods 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 150000001945 cysteines Chemical group 0.000 description 3
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 239000012149 elution buffer Substances 0.000 description 3
- 238000012869 ethanol precipitation Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 238000002523 gelfiltration Methods 0.000 description 3
- 102000005396 glutamine synthetase Human genes 0.000 description 3
- 108020002326 glutamine synthetase Proteins 0.000 description 3
- 239000000710 homodimer Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000010354 integration Effects 0.000 description 3
- 238000001155 isoelectric focusing Methods 0.000 description 3
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 229960004927 neomycin Drugs 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 230000017854 proteolysis Effects 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 230000003248 secreting effect Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 229910052720 vanadium Inorganic materials 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- 102100036933 12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid receptor Human genes 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 2
- DVLFYONBTKHTER-UHFFFAOYSA-N 3-(N-morpholino)propanesulfonic acid Chemical compound OS(=O)(=O)CCCN1CCOCC1 DVLFYONBTKHTER-UHFFFAOYSA-N 0.000 description 2
- SXXLKZCNJHJYFL-UHFFFAOYSA-N 4,5,6,7-tetrahydro-[1,2]oxazolo[4,5-c]pyridin-5-ium-3-olate Chemical compound C1CNCC2=C1ONC2=O SXXLKZCNJHJYFL-UHFFFAOYSA-N 0.000 description 2
- 108010082808 4-1BB Ligand Proteins 0.000 description 2
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 101710154825 Aminoglycoside 3'-phosphotransferase Proteins 0.000 description 2
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 2
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 2
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 2
- 102100022717 Atypical chemokine receptor 1 Human genes 0.000 description 2
- 108091008875 B cell receptors Proteins 0.000 description 2
- 108010028006 B-Cell Activating Factor Proteins 0.000 description 2
- 102100038080 B-cell receptor CD22 Human genes 0.000 description 2
- 102100023995 Beta-nerve growth factor Human genes 0.000 description 2
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 2
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 description 2
- 102100022525 Bone morphogenetic protein 6 Human genes 0.000 description 2
- 102100022545 Bone morphogenetic protein 8B Human genes 0.000 description 2
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 2
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 2
- 102100031174 C-C chemokine receptor type 10 Human genes 0.000 description 2
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 2
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 2
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 2
- 101710149863 C-C chemokine receptor type 4 Proteins 0.000 description 2
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 2
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 2
- 102100036305 C-C chemokine receptor type 8 Human genes 0.000 description 2
- 102100036303 C-C chemokine receptor type 9 Human genes 0.000 description 2
- 102100025074 C-C chemokine receptor-like 2 Human genes 0.000 description 2
- 101710112613 C-C motif chemokine 13 Proteins 0.000 description 2
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 2
- 101710112538 C-C motif chemokine 27 Proteins 0.000 description 2
- 101710155834 C-C motif chemokine 7 Proteins 0.000 description 2
- 102100034871 C-C motif chemokine 8 Human genes 0.000 description 2
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 description 2
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 2
- 102100025277 C-X-C motif chemokine 13 Human genes 0.000 description 2
- 102100025250 C-X-C motif chemokine 14 Human genes 0.000 description 2
- 102100039396 C-X-C motif chemokine 16 Human genes 0.000 description 2
- 101710085504 C-X-C motif chemokine 6 Proteins 0.000 description 2
- 101710085500 C-X-C motif chemokine 9 Proteins 0.000 description 2
- 102100032957 C5a anaphylatoxin chemotactic receptor 1 Human genes 0.000 description 2
- 108010046080 CD27 Ligand Proteins 0.000 description 2
- 108010017987 CD30 Ligand Proteins 0.000 description 2
- 102100032912 CD44 antigen Human genes 0.000 description 2
- 102100040527 CKLF-like MARVEL transmembrane domain-containing protein 3 Human genes 0.000 description 2
- 102100040529 CKLF-like MARVEL transmembrane domain-containing protein 4 Human genes 0.000 description 2
- 102100040525 CKLF-like MARVEL transmembrane domain-containing protein 5 Human genes 0.000 description 2
- 102100040528 CKLF-like MARVEL transmembrane domain-containing protein 6 Human genes 0.000 description 2
- 102100040855 CKLF-like MARVEL transmembrane domain-containing protein 7 Human genes 0.000 description 2
- 108090000835 CX3C Chemokine Receptor 1 Proteins 0.000 description 2
- 108010061304 CXCR6 Receptors Proteins 0.000 description 2
- 102100022480 Cadherin-20 Human genes 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- 108010083647 Chemokine CCL24 Proteins 0.000 description 2
- 108010083698 Chemokine CCL26 Proteins 0.000 description 2
- 108010055166 Chemokine CCL5 Proteins 0.000 description 2
- 102100035294 Chemokine XC receptor 1 Human genes 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 102100032887 Clusterin Human genes 0.000 description 2
- 108090000197 Clusterin Proteins 0.000 description 2
- 241000699802 Cricetulus griseus Species 0.000 description 2
- 102100036329 Cyclin-dependent kinase 3 Human genes 0.000 description 2
- 102100035298 Cytokine SCM-1 beta Human genes 0.000 description 2
- 102100026234 Cytokine receptor common subunit gamma Human genes 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 101710146739 Enterotoxin Proteins 0.000 description 2
- 102100023688 Eotaxin Human genes 0.000 description 2
- 101710139422 Eotaxin Proteins 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 2
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 2
- 102100035292 Fibroblast growth factor 14 Human genes 0.000 description 2
- 102100035307 Fibroblast growth factor 16 Human genes 0.000 description 2
- 108050002072 Fibroblast growth factor 16 Proteins 0.000 description 2
- 108090000381 Fibroblast growth factor 4 Proteins 0.000 description 2
- 102100028075 Fibroblast growth factor 6 Human genes 0.000 description 2
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 2
- 108090000368 Fibroblast growth factor 8 Proteins 0.000 description 2
- 102100037665 Fibroblast growth factor 9 Human genes 0.000 description 2
- 102100020997 Fractalkine Human genes 0.000 description 2
- 101150019176 GDF10 gene Proteins 0.000 description 2
- 101710115997 Gamma-tubulin complex component 2 Proteins 0.000 description 2
- 102000004878 Gelsolin Human genes 0.000 description 2
- 108090001064 Gelsolin Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 102100040895 Growth/differentiation factor 10 Human genes 0.000 description 2
- 102100035379 Growth/differentiation factor 5 Human genes 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101001071349 Homo sapiens 12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid receptor Proteins 0.000 description 2
- 101000678879 Homo sapiens Atypical chemokine receptor 1 Proteins 0.000 description 2
- 101000798902 Homo sapiens Atypical chemokine receptor 4 Proteins 0.000 description 2
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 2
- 101001111439 Homo sapiens Beta-nerve growth factor Proteins 0.000 description 2
- 101000762366 Homo sapiens Bone morphogenetic protein 2 Proteins 0.000 description 2
- 101000762379 Homo sapiens Bone morphogenetic protein 4 Proteins 0.000 description 2
- 101000899390 Homo sapiens Bone morphogenetic protein 6 Proteins 0.000 description 2
- 101000899368 Homo sapiens Bone morphogenetic protein 8B Proteins 0.000 description 2
- 101000777558 Homo sapiens C-C chemokine receptor type 10 Proteins 0.000 description 2
- 101000980744 Homo sapiens C-C chemokine receptor type 3 Proteins 0.000 description 2
- 101000738584 Homo sapiens C-C chemokine receptor type 4 Proteins 0.000 description 2
- 101000946926 Homo sapiens C-C chemokine receptor type 5 Proteins 0.000 description 2
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 description 2
- 101000716063 Homo sapiens C-C chemokine receptor type 8 Proteins 0.000 description 2
- 101000934394 Homo sapiens C-C chemokine receptor-like 2 Proteins 0.000 description 2
- 101000978379 Homo sapiens C-C motif chemokine 13 Proteins 0.000 description 2
- 101000897493 Homo sapiens C-C motif chemokine 26 Proteins 0.000 description 2
- 101000797762 Homo sapiens C-C motif chemokine 5 Proteins 0.000 description 2
- 101000797758 Homo sapiens C-C motif chemokine 7 Proteins 0.000 description 2
- 101000946794 Homo sapiens C-C motif chemokine 8 Proteins 0.000 description 2
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 description 2
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 2
- 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 description 2
- 101000858060 Homo sapiens C-X-C motif chemokine 11 Proteins 0.000 description 2
- 101000858064 Homo sapiens C-X-C motif chemokine 13 Proteins 0.000 description 2
- 101000858068 Homo sapiens C-X-C motif chemokine 14 Proteins 0.000 description 2
- 101000889133 Homo sapiens C-X-C motif chemokine 16 Proteins 0.000 description 2
- 101000947177 Homo sapiens C-X-C motif chemokine 6 Proteins 0.000 description 2
- 101000947172 Homo sapiens C-X-C motif chemokine 9 Proteins 0.000 description 2
- 101000867983 Homo sapiens C5a anaphylatoxin chemotactic receptor 1 Proteins 0.000 description 2
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 description 2
- 101000749433 Homo sapiens CKLF-like MARVEL transmembrane domain-containing protein 3 Proteins 0.000 description 2
- 101000749431 Homo sapiens CKLF-like MARVEL transmembrane domain-containing protein 4 Proteins 0.000 description 2
- 101000749437 Homo sapiens CKLF-like MARVEL transmembrane domain-containing protein 5 Proteins 0.000 description 2
- 101000749435 Homo sapiens CKLF-like MARVEL transmembrane domain-containing protein 6 Proteins 0.000 description 2
- 101000749308 Homo sapiens CKLF-like MARVEL transmembrane domain-containing protein 7 Proteins 0.000 description 2
- 101000899410 Homo sapiens Cadherin-19 Proteins 0.000 description 2
- 101000899459 Homo sapiens Cadherin-20 Proteins 0.000 description 2
- 101000804783 Homo sapiens Chemokine XC receptor 1 Proteins 0.000 description 2
- 101000804771 Homo sapiens Cytokine SCM-1 beta Proteins 0.000 description 2
- 101001055227 Homo sapiens Cytokine receptor common subunit gamma Proteins 0.000 description 2
- 101000878181 Homo sapiens Fibroblast growth factor 14 Proteins 0.000 description 2
- 101001060274 Homo sapiens Fibroblast growth factor 4 Proteins 0.000 description 2
- 101001060261 Homo sapiens Fibroblast growth factor 7 Proteins 0.000 description 2
- 101001027380 Homo sapiens Fibroblast growth factor 9 Proteins 0.000 description 2
- 101000854520 Homo sapiens Fractalkine Proteins 0.000 description 2
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 2
- 101001023988 Homo sapiens Growth/differentiation factor 5 Proteins 0.000 description 2
- 101001035752 Homo sapiens Hydroxycarboxylic acid receptor 3 Proteins 0.000 description 2
- 101000998783 Homo sapiens Insulin-like 3 Proteins 0.000 description 2
- 101000959794 Homo sapiens Interferon alpha-2 Proteins 0.000 description 2
- 101000959708 Homo sapiens Interferon alpha-4 Proteins 0.000 description 2
- 101000959704 Homo sapiens Interferon alpha-5 Proteins 0.000 description 2
- 101000959714 Homo sapiens Interferon alpha-6 Proteins 0.000 description 2
- 101000961126 Homo sapiens Interferon alpha-7 Proteins 0.000 description 2
- 101001002470 Homo sapiens Interferon lambda-1 Proteins 0.000 description 2
- 101001002469 Homo sapiens Interferon lambda-2 Proteins 0.000 description 2
- 101001002466 Homo sapiens Interferon lambda-3 Proteins 0.000 description 2
- 101000960952 Homo sapiens Interleukin-1 receptor accessory protein Proteins 0.000 description 2
- 101001076407 Homo sapiens Interleukin-1 receptor antagonist protein Proteins 0.000 description 2
- 101000852965 Homo sapiens Interleukin-1 receptor-like 2 Proteins 0.000 description 2
- 101001003142 Homo sapiens Interleukin-12 receptor subunit beta-1 Proteins 0.000 description 2
- 101001010600 Homo sapiens Interleukin-12 subunit alpha Proteins 0.000 description 2
- 101000852992 Homo sapiens Interleukin-12 subunit beta Proteins 0.000 description 2
- 101000998181 Homo sapiens Interleukin-17B Proteins 0.000 description 2
- 101001019615 Homo sapiens Interleukin-18 receptor accessory protein Proteins 0.000 description 2
- 101001019591 Homo sapiens Interleukin-18-binding protein Proteins 0.000 description 2
- 101000960946 Homo sapiens Interleukin-19 Proteins 0.000 description 2
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 2
- 101001055145 Homo sapiens Interleukin-2 receptor subunit beta Proteins 0.000 description 2
- 101000853002 Homo sapiens Interleukin-25 Proteins 0.000 description 2
- 101000853000 Homo sapiens Interleukin-26 Proteins 0.000 description 2
- 101000852998 Homo sapiens Interleukin-27 subunit alpha Proteins 0.000 description 2
- 101001033279 Homo sapiens Interleukin-3 Proteins 0.000 description 2
- 101000998120 Homo sapiens Interleukin-3 receptor subunit alpha Proteins 0.000 description 2
- 101000998126 Homo sapiens Interleukin-36 beta Proteins 0.000 description 2
- 101001040964 Homo sapiens Interleukin-36 receptor antagonist protein Proteins 0.000 description 2
- 101001033312 Homo sapiens Interleukin-4 receptor subunit alpha Proteins 0.000 description 2
- 101000960936 Homo sapiens Interleukin-5 receptor subunit alpha Proteins 0.000 description 2
- 101000599056 Homo sapiens Interleukin-6 receptor subunit beta Proteins 0.000 description 2
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 2
- 101000947178 Homo sapiens Platelet basic protein Proteins 0.000 description 2
- 101000655540 Homo sapiens Protransforming growth factor alpha Proteins 0.000 description 2
- 101000668165 Homo sapiens RNA-binding motif, single-stranded-interacting protein 1 Proteins 0.000 description 2
- 101000651890 Homo sapiens Slit homolog 2 protein Proteins 0.000 description 2
- 101000651893 Homo sapiens Slit homolog 3 protein Proteins 0.000 description 2
- 101000617130 Homo sapiens Stromal cell-derived factor 1 Proteins 0.000 description 2
- 101000684994 Homo sapiens Stromal cell-derived factor 2 Proteins 0.000 description 2
- 101000874179 Homo sapiens Syndecan-1 Proteins 0.000 description 2
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 2
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 2
- 101000799461 Homo sapiens Thrombopoietin Proteins 0.000 description 2
- 101000831567 Homo sapiens Toll-like receptor 2 Proteins 0.000 description 2
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 2
- 101000635958 Homo sapiens Transforming growth factor beta-2 proprotein Proteins 0.000 description 2
- 101000894525 Homo sapiens Transforming growth factor-beta-induced protein ig-h3 Proteins 0.000 description 2
- 101000795117 Homo sapiens Triggering receptor expressed on myeloid cells 2 Proteins 0.000 description 2
- 101000830600 Homo sapiens Tumor necrosis factor ligand superfamily member 13 Proteins 0.000 description 2
- 101000830596 Homo sapiens Tumor necrosis factor ligand superfamily member 15 Proteins 0.000 description 2
- 101000638161 Homo sapiens Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 2
- 101000638255 Homo sapiens Tumor necrosis factor ligand superfamily member 8 Proteins 0.000 description 2
- 101000638251 Homo sapiens Tumor necrosis factor ligand superfamily member 9 Proteins 0.000 description 2
- 101000994810 Homo sapiens X-linked interleukin-1 receptor accessory protein-like 2 Proteins 0.000 description 2
- 101001026578 Hordeum vulgare Ent-kaurenoic acid oxidase 1 Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102100039356 Hydroxycarboxylic acid receptor 3 Human genes 0.000 description 2
- 108091058560 IL8 Proteins 0.000 description 2
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 2
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 102100033262 Insulin-like 3 Human genes 0.000 description 2
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 2
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 2
- 102100040018 Interferon alpha-2 Human genes 0.000 description 2
- 102100039949 Interferon alpha-4 Human genes 0.000 description 2
- 102100039948 Interferon alpha-5 Human genes 0.000 description 2
- 102100040007 Interferon alpha-6 Human genes 0.000 description 2
- 102100039350 Interferon alpha-7 Human genes 0.000 description 2
- 102100020990 Interferon lambda-1 Human genes 0.000 description 2
- 102100020989 Interferon lambda-2 Human genes 0.000 description 2
- 102100020992 Interferon lambda-3 Human genes 0.000 description 2
- 108700003107 Interleukin-1 Receptor-Like 1 Proteins 0.000 description 2
- 102100020881 Interleukin-1 alpha Human genes 0.000 description 2
- 102100039880 Interleukin-1 receptor accessory protein Human genes 0.000 description 2
- 102100036706 Interleukin-1 receptor-like 1 Human genes 0.000 description 2
- 102100036697 Interleukin-1 receptor-like 2 Human genes 0.000 description 2
- 102100020790 Interleukin-12 receptor subunit beta-1 Human genes 0.000 description 2
- 102100030698 Interleukin-12 subunit alpha Human genes 0.000 description 2
- 102100036701 Interleukin-12 subunit beta Human genes 0.000 description 2
- 102100033101 Interleukin-17B Human genes 0.000 description 2
- 102100035010 Interleukin-18 receptor accessory protein Human genes 0.000 description 2
- 102100035017 Interleukin-18-binding protein Human genes 0.000 description 2
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 2
- 102100026879 Interleukin-2 receptor subunit beta Human genes 0.000 description 2
- 108010065637 Interleukin-23 Proteins 0.000 description 2
- 102100036680 Interleukin-25 Human genes 0.000 description 2
- 102100036679 Interleukin-26 Human genes 0.000 description 2
- 108010066979 Interleukin-27 Proteins 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- 102100033493 Interleukin-3 receptor subunit alpha Human genes 0.000 description 2
- 102100033498 Interleukin-36 beta Human genes 0.000 description 2
- 102100021150 Interleukin-36 receptor antagonist protein Human genes 0.000 description 2
- 102100033502 Interleukin-37 Human genes 0.000 description 2
- 102100039078 Interleukin-4 receptor subunit alpha Human genes 0.000 description 2
- 102100039881 Interleukin-5 receptor subunit alpha Human genes 0.000 description 2
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 2
- 102100026244 Interleukin-9 receptor Human genes 0.000 description 2
- 102100033420 Keratin, type I cytoskeletal 19 Human genes 0.000 description 2
- 125000002059 L-arginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 108090000364 Ligases Proteins 0.000 description 2
- 101001089108 Lotus tetragonolobus Anti-H(O) lectin Proteins 0.000 description 2
- 102100035304 Lymphotactin Human genes 0.000 description 2
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 2
- 102100037273 Mammaglobin-A Human genes 0.000 description 2
- 102100037267 Mammaglobin-B Human genes 0.000 description 2
- 102000003792 Metallothionein Human genes 0.000 description 2
- 102100030335 Midkine Human genes 0.000 description 2
- 101000934396 Mus musculus C-C chemokine receptor-like 2 Proteins 0.000 description 2
- 101100005657 Mus musculus Ccr7 gene Proteins 0.000 description 2
- 101100446506 Mus musculus Fgf3 gene Proteins 0.000 description 2
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 2
- 101100027996 Mus musculus Omg gene Proteins 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 108090000526 Papain Proteins 0.000 description 2
- 108090000284 Pepsin A Proteins 0.000 description 2
- 102000057297 Pepsin A Human genes 0.000 description 2
- 206010057249 Phagocytosis Diseases 0.000 description 2
- 102100036154 Platelet basic protein Human genes 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 2
- 102100032350 Protransforming growth factor alpha Human genes 0.000 description 2
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 2
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 2
- 101710148333 Regulator of G-protein signaling 13 Proteins 0.000 description 2
- 102100021035 Regulator of G-protein signaling 18 Human genes 0.000 description 2
- 102100037415 Regulator of G-protein signaling 3 Human genes 0.000 description 2
- 101710140411 Regulator of G-protein signaling 3 Proteins 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- 241000607720 Serratia Species 0.000 description 2
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 2
- 102100027339 Slit homolog 3 protein Human genes 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 description 2
- 102100023184 Stromal cell-derived factor 2 Human genes 0.000 description 2
- 102100035721 Syndecan-1 Human genes 0.000 description 2
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 2
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 102100034195 Thrombopoietin Human genes 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 102000006601 Thymidine Kinase Human genes 0.000 description 2
- 108020004440 Thymidine kinase Proteins 0.000 description 2
- 102100024333 Toll-like receptor 2 Human genes 0.000 description 2
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- 102100030737 Transforming growth factor beta-2 proprotein Human genes 0.000 description 2
- 102000056172 Transforming growth factor beta-3 Human genes 0.000 description 2
- 108090000097 Transforming growth factor beta-3 Proteins 0.000 description 2
- 102100021398 Transforming growth factor-beta-induced protein ig-h3 Human genes 0.000 description 2
- 102100029678 Triggering receptor expressed on myeloid cells 2 Human genes 0.000 description 2
- 101710097155 Tumor necrosis factor ligand superfamily member 12 Proteins 0.000 description 2
- 102100024585 Tumor necrosis factor ligand superfamily member 13 Human genes 0.000 description 2
- 102100024587 Tumor necrosis factor ligand superfamily member 15 Human genes 0.000 description 2
- 102100026890 Tumor necrosis factor ligand superfamily member 4 Human genes 0.000 description 2
- 102100033725 Tumor necrosis factor receptor superfamily member 16 Human genes 0.000 description 2
- 101710187751 Tumor necrosis factor receptor superfamily member 21 Proteins 0.000 description 2
- 108091008605 VEGF receptors Proteins 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 102100038234 Vascular endothelial growth factor D Human genes 0.000 description 2
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 2
- 108020005202 Viral DNA Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 102100034412 X-linked interleukin-1 receptor accessory protein-like 2 Human genes 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 2
- 238000000137 annealing Methods 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- KMGARVOVYXNAOF-UHFFFAOYSA-N benzpiperylone Chemical compound C1CN(C)CCC1N1C(=O)C(CC=2C=CC=CC=2)=C(C=2C=CC=CC=2)N1 KMGARVOVYXNAOF-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 2
- 229960003669 carbenicillin Drugs 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000007910 cell fusion Effects 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 230000003196 chaotropic effect Effects 0.000 description 2
- 238000012412 chemical coupling Methods 0.000 description 2
- 238000010382 chemical cross-linking Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- FOCAHLGSDWHSAH-UHFFFAOYSA-N difluoromethanethione Chemical compound FC(F)=S FOCAHLGSDWHSAH-UHFFFAOYSA-N 0.000 description 2
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
- 150000002019 disulfides Chemical class 0.000 description 2
- 239000000147 enterotoxin Substances 0.000 description 2
- 231100000655 enterotoxin Toxicity 0.000 description 2
- DUYAAUVXQSMXQP-UHFFFAOYSA-N ethanethioic S-acid Chemical compound CC(S)=O DUYAAUVXQSMXQP-UHFFFAOYSA-N 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000011536 extraction buffer Substances 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 229940045883 glutathione disulfide Drugs 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 102000004311 liver X receptors Human genes 0.000 description 2
- 108090000865 liver X receptors Proteins 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 108010019677 lymphotactin Proteins 0.000 description 2
- AEUKDPKXTPNBNY-XEYRWQBLSA-N mcp 2 Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)C1=CC=CC=C1 AEUKDPKXTPNBNY-XEYRWQBLSA-N 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000007758 minimum essential medium Substances 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 229940055729 papain Drugs 0.000 description 2
- 235000019834 papain Nutrition 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229940111202 pepsin Drugs 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 210000001322 periplasm Anatomy 0.000 description 2
- 230000008782 phagocytosis Effects 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- CCTIOCVIZPCTGO-BYPYZUCNSA-N phosphoarginine Chemical group OC(=O)[C@@H](N)CCCNC(=N)NP(O)(O)=O CCTIOCVIZPCTGO-BYPYZUCNSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000001742 protein purification Methods 0.000 description 2
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 2
- 230000005180 public health Effects 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 238000003156 radioimmunoprecipitation Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 238000009987 spinning Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 2
- 235000019798 tripotassium phosphate Nutrition 0.000 description 2
- 108010087967 type I signal peptidase Proteins 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 241001515965 unidentified phage Species 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- LJJFNFYPZOHRHM-UHFFFAOYSA-N 1-isocyano-2-methoxy-2-methylpropane Chemical compound COC(C)(C)C[N+]#[C-] LJJFNFYPZOHRHM-UHFFFAOYSA-N 0.000 description 1
- SXGZJKUKBWWHRA-UHFFFAOYSA-N 2-(N-morpholiniumyl)ethanesulfonate Chemical compound [O-]S(=O)(=O)CC[NH+]1CCOCC1 SXGZJKUKBWWHRA-UHFFFAOYSA-N 0.000 description 1
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 description 1
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
- 102100022464 5'-nucleotidase Human genes 0.000 description 1
- WBSMIPAMAXNXFS-UHFFFAOYSA-N 5-Nitro-2-(3-phenylpropylamino)benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NCCCC1=CC=CC=C1 WBSMIPAMAXNXFS-UHFFFAOYSA-N 0.000 description 1
- 101710142585 50S ribosomal protein 6, chloroplastic Proteins 0.000 description 1
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 1
- 102100031901 A-kinase anchor protein 2 Human genes 0.000 description 1
- 101150054149 ANGPTL4 gene Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102100028249 Acetyl-coenzyme A transporter 1 Human genes 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102100021886 Activin receptor type-2A Human genes 0.000 description 1
- 102100027647 Activin receptor type-2B Human genes 0.000 description 1
- 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 1
- 102100036664 Adenosine deaminase Human genes 0.000 description 1
- 102100036601 Aggrecan core protein Human genes 0.000 description 1
- 108010067219 Aggrecans Proteins 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 102100022524 Alpha-1-antichymotrypsin Human genes 0.000 description 1
- 102100023635 Alpha-fetoprotein Human genes 0.000 description 1
- 102100026882 Alpha-synuclein Human genes 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 108700042530 Angiopoietin-Like Protein 4 Proteins 0.000 description 1
- 102100025668 Angiopoietin-related protein 3 Human genes 0.000 description 1
- 102100025674 Angiopoietin-related protein 4 Human genes 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 101100351711 Arabidopsis thaliana PEX14 gene Proteins 0.000 description 1
- 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 1
- 241000203069 Archaea Species 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 101001099569 Aspergillus oryzae (strain ATCC 42149 / RIB 40) Pectin lyase 1 Proteins 0.000 description 1
- 241000713842 Avian sarcoma virus Species 0.000 description 1
- 102100027205 B-cell antigen receptor complex-associated protein alpha chain Human genes 0.000 description 1
- 102100027203 B-cell antigen receptor complex-associated protein beta chain Human genes 0.000 description 1
- 102100025218 B-cell differentiation antigen CD72 Human genes 0.000 description 1
- 102100021631 B-cell lymphoma 6 protein Human genes 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 108091012583 BCL2 Proteins 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 102100021257 Beta-secretase 1 Human genes 0.000 description 1
- 102100021277 Beta-secretase 2 Human genes 0.000 description 1
- 102100038495 Bile acid receptor Human genes 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 1
- 102100036841 C-C motif chemokine 1 Human genes 0.000 description 1
- 102100023703 C-C motif chemokine 15 Human genes 0.000 description 1
- 102100031658 C-X-C chemokine receptor type 5 Human genes 0.000 description 1
- 101710098275 C-X-C motif chemokine 10 Proteins 0.000 description 1
- 101710098272 C-X-C motif chemokine 11 Proteins 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 1
- 102100034798 CCAAT/enhancer-binding protein beta Human genes 0.000 description 1
- 102100027207 CD27 antigen Human genes 0.000 description 1
- 108010065524 CD52 Antigen Proteins 0.000 description 1
- 102100027221 CD81 antigen Human genes 0.000 description 1
- 102100035793 CD83 antigen Human genes 0.000 description 1
- 102100040531 CKLF-like MARVEL transmembrane domain-containing protein 2 Human genes 0.000 description 1
- 102100039553 CKLF-like MARVEL transmembrane domain-containing protein 8 Human genes 0.000 description 1
- 102000000905 Cadherin Human genes 0.000 description 1
- 108050007957 Cadherin Proteins 0.000 description 1
- 102100024156 Cadherin-12 Human genes 0.000 description 1
- 102100024154 Cadherin-13 Human genes 0.000 description 1
- 102100022527 Cadherin-18 Human genes 0.000 description 1
- 102100022529 Cadherin-19 Human genes 0.000 description 1
- 102100029761 Cadherin-5 Human genes 0.000 description 1
- 102100025331 Cadherin-8 Human genes 0.000 description 1
- 102100025332 Cadherin-9 Human genes 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 101100293794 Canis lupus familiaris NME1 gene Proteins 0.000 description 1
- 101001110283 Canis lupus familiaris Ras-related C3 botulinum toxin substrate 1 Proteins 0.000 description 1
- 102100032145 Carbohydrate sulfotransferase 10 Human genes 0.000 description 1
- 102100033377 Carbohydrate sulfotransferase 15 Human genes 0.000 description 1
- 102000004018 Caspase 6 Human genes 0.000 description 1
- 108090000425 Caspase 6 Proteins 0.000 description 1
- 102100035904 Caspase-1 Human genes 0.000 description 1
- 102100025597 Caspase-4 Human genes 0.000 description 1
- 108090000712 Cathepsin B Proteins 0.000 description 1
- 102000004225 Cathepsin B Human genes 0.000 description 1
- 102100021633 Cathepsin B Human genes 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 102000009410 Chemokine receptor Human genes 0.000 description 1
- 108050000299 Chemokine receptor Proteins 0.000 description 1
- 101100004180 Chironomus tentans BR3 gene Proteins 0.000 description 1
- 102000012286 Chitinases Human genes 0.000 description 1
- 108010022172 Chitinases Proteins 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 108010038447 Chromogranin A Proteins 0.000 description 1
- 102100031186 Chromogranin-A Human genes 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- 102100038423 Claudin-3 Human genes 0.000 description 1
- 102100026098 Claudin-7 Human genes 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 102100031162 Collagen alpha-1(XVIII) chain Human genes 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- 102100025191 Cyclin-A2 Human genes 0.000 description 1
- 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 1
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 1
- 108010025454 Cyclin-Dependent Kinase 5 Proteins 0.000 description 1
- 108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 description 1
- 108010009356 Cyclin-Dependent Kinase Inhibitor p15 Proteins 0.000 description 1
- 102000009512 Cyclin-Dependent Kinase Inhibitor p15 Human genes 0.000 description 1
- 108010009367 Cyclin-Dependent Kinase Inhibitor p18 Proteins 0.000 description 1
- 102000009503 Cyclin-Dependent Kinase Inhibitor p18 Human genes 0.000 description 1
- 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 1
- 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 1
- 102100026804 Cyclin-dependent kinase 6 Human genes 0.000 description 1
- 102100026810 Cyclin-dependent kinase 7 Human genes 0.000 description 1
- 102100024457 Cyclin-dependent kinase 9 Human genes 0.000 description 1
- 102100026805 Cyclin-dependent-like kinase 5 Human genes 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 1
- 108010005843 Cysteine Proteases Proteins 0.000 description 1
- 102000005927 Cysteine Proteases Human genes 0.000 description 1
- 102100031655 Cytochrome b5 Human genes 0.000 description 1
- 102100036952 Cytoplasmic protein NCK2 Human genes 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 102100033587 DNA topoisomerase 2-alpha Human genes 0.000 description 1
- 101100285402 Danio rerio eng1a gene Proteins 0.000 description 1
- 101100481404 Danio rerio tie1 gene Proteins 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
- 102100028571 Disabled homolog 2-interacting protein Human genes 0.000 description 1
- 102100024364 Disintegrin and metalloproteinase domain-containing protein 8 Human genes 0.000 description 1
- 241000255601 Drosophila melanogaster Species 0.000 description 1
- 101100278839 Drosophila melanogaster sw gene Proteins 0.000 description 1
- 102100023332 Dual specificity mitogen-activated protein kinase kinase 7 Human genes 0.000 description 1
- 102100036254 E3 SUMO-protein ligase PIAS2 Human genes 0.000 description 1
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 1
- 102100033267 Early placenta insulin-like peptide Human genes 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 241000305071 Enterobacterales Species 0.000 description 1
- 102100029727 Enteropeptidase Human genes 0.000 description 1
- 108010013369 Enteropeptidase Proteins 0.000 description 1
- 102100033940 Ephrin-A3 Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 1
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 101000617479 Escherichia coli (strain K12) PTS system fructose-like EIIA component Proteins 0.000 description 1
- 101100409165 Escherichia coli (strain K12) prc gene Proteins 0.000 description 1
- 241001522878 Escherichia coli B Species 0.000 description 1
- 102100029951 Estrogen receptor beta Human genes 0.000 description 1
- 102100026693 FAS-associated death domain protein Human genes 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- 102100028412 Fibroblast growth factor 10 Human genes 0.000 description 1
- 102100035308 Fibroblast growth factor 17 Human genes 0.000 description 1
- 102100031734 Fibroblast growth factor 19 Human genes 0.000 description 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 102100031361 Fibroblast growth factor 20 Human genes 0.000 description 1
- 108090000376 Fibroblast growth factor 21 Proteins 0.000 description 1
- 102000003973 Fibroblast growth factor 21 Human genes 0.000 description 1
- 102100024802 Fibroblast growth factor 23 Human genes 0.000 description 1
- 102100028073 Fibroblast growth factor 5 Human genes 0.000 description 1
- 108090000382 Fibroblast growth factor 6 Proteins 0.000 description 1
- 102100037680 Fibroblast growth factor 8 Human genes 0.000 description 1
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 1
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 241000700662 Fowlpox virus Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 102100037854 G1/S-specific cyclin-E2 Human genes 0.000 description 1
- 102000017700 GABRP Human genes 0.000 description 1
- 241000251129 Galeocerdo Species 0.000 description 1
- 108700023863 Gene Components Proteins 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 102000058058 Glucose Transporter Type 2 Human genes 0.000 description 1
- 102100033366 Glutathione hydrolase 1 proenzyme Human genes 0.000 description 1
- YWAQATDNEKZFFK-BYPYZUCNSA-N Gly-Gly-Ser Chemical group NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O YWAQATDNEKZFFK-BYPYZUCNSA-N 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 description 1
- 102100030595 HLA class II histocompatibility antigen gamma chain Human genes 0.000 description 1
- 102100040505 HLA class II histocompatibility antigen, DR alpha chain Human genes 0.000 description 1
- 108010075704 HLA-A Antigens Proteins 0.000 description 1
- 108010067802 HLA-DR alpha-Chains Proteins 0.000 description 1
- 101100082540 Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) pcp gene Proteins 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 108010007707 Hepatitis A Virus Cellular Receptor 2 Proteins 0.000 description 1
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 102100034676 Hepatocyte cell adhesion molecule Human genes 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 102100038006 High affinity immunoglobulin epsilon receptor subunit alpha Human genes 0.000 description 1
- 102100021454 Histone deacetylase 4 Human genes 0.000 description 1
- 102100021453 Histone deacetylase 5 Human genes 0.000 description 1
- 102100038719 Histone deacetylase 7 Human genes 0.000 description 1
- 102100038720 Histone deacetylase 9 Human genes 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 101000678236 Homo sapiens 5'-nucleotidase Proteins 0.000 description 1
- 101000627872 Homo sapiens 72 kDa type IV collagenase Proteins 0.000 description 1
- 101000774738 Homo sapiens A-kinase anchor protein 2 Proteins 0.000 description 1
- 101000970954 Homo sapiens Activin receptor type-2A Proteins 0.000 description 1
- 101000937269 Homo sapiens Activin receptor type-2B Proteins 0.000 description 1
- 101000824278 Homo sapiens Acyl-[acyl-carrier-protein] hydrolase Proteins 0.000 description 1
- 101000678026 Homo sapiens Alpha-1-antichymotrypsin Proteins 0.000 description 1
- 101000693085 Homo sapiens Angiopoietin-related protein 3 Proteins 0.000 description 1
- 101000914489 Homo sapiens B-cell antigen receptor complex-associated protein alpha chain Proteins 0.000 description 1
- 101000914491 Homo sapiens B-cell antigen receptor complex-associated protein beta chain Proteins 0.000 description 1
- 101000934359 Homo sapiens B-cell differentiation antigen CD72 Proteins 0.000 description 1
- 101000971234 Homo sapiens B-cell lymphoma 6 protein Proteins 0.000 description 1
- 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 description 1
- 101000894883 Homo sapiens Beta-secretase 2 Proteins 0.000 description 1
- 101000603876 Homo sapiens Bile acid receptor Proteins 0.000 description 1
- 101000978376 Homo sapiens C-C motif chemokine 15 Proteins 0.000 description 1
- 101000922405 Homo sapiens C-X-C chemokine receptor type 5 Proteins 0.000 description 1
- 101000945963 Homo sapiens CCAAT/enhancer-binding protein beta Proteins 0.000 description 1
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 1
- 101000868215 Homo sapiens CD40 ligand Proteins 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 101000914479 Homo sapiens CD81 antigen Proteins 0.000 description 1
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 1
- 101000749427 Homo sapiens CKLF-like MARVEL transmembrane domain-containing protein 2 Proteins 0.000 description 1
- 101000888512 Homo sapiens CKLF-like MARVEL transmembrane domain-containing protein 8 Proteins 0.000 description 1
- 101000762238 Homo sapiens Cadherin-12 Proteins 0.000 description 1
- 101000762243 Homo sapiens Cadherin-13 Proteins 0.000 description 1
- 101000899405 Homo sapiens Cadherin-18 Proteins 0.000 description 1
- 101000794587 Homo sapiens Cadherin-5 Proteins 0.000 description 1
- 101000935111 Homo sapiens Cadherin-7 Proteins 0.000 description 1
- 101000935095 Homo sapiens Cadherin-8 Proteins 0.000 description 1
- 101000935098 Homo sapiens Cadherin-9 Proteins 0.000 description 1
- 101000775595 Homo sapiens Carbohydrate sulfotransferase 10 Proteins 0.000 description 1
- 101000715398 Homo sapiens Caspase-1 Proteins 0.000 description 1
- 101000933112 Homo sapiens Caspase-4 Proteins 0.000 description 1
- 101000898449 Homo sapiens Cathepsin B Proteins 0.000 description 1
- 101000882908 Homo sapiens Claudin-3 Proteins 0.000 description 1
- 101000912652 Homo sapiens Claudin-7 Proteins 0.000 description 1
- 101000940068 Homo sapiens Collagen alpha-1(XVIII) chain Proteins 0.000 description 1
- 101000934320 Homo sapiens Cyclin-A2 Proteins 0.000 description 1
- 101000715946 Homo sapiens Cyclin-dependent kinase 3 Proteins 0.000 description 1
- 101000911952 Homo sapiens Cyclin-dependent kinase 7 Proteins 0.000 description 1
- 101000980930 Homo sapiens Cyclin-dependent kinase 9 Proteins 0.000 description 1
- 101000945639 Homo sapiens Cyclin-dependent kinase inhibitor 3 Proteins 0.000 description 1
- 101000922386 Homo sapiens Cytochrome b5 Proteins 0.000 description 1
- 101001024712 Homo sapiens Cytoplasmic protein NCK2 Proteins 0.000 description 1
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 1
- 101000908391 Homo sapiens Dipeptidyl peptidase 4 Proteins 0.000 description 1
- 101000915396 Homo sapiens Disabled homolog 2-interacting protein Proteins 0.000 description 1
- 101000832767 Homo sapiens Disintegrin and metalloproteinase domain-containing protein 8 Proteins 0.000 description 1
- 101000624594 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 7 Proteins 0.000 description 1
- 101001074629 Homo sapiens E3 SUMO-protein ligase PIAS2 Proteins 0.000 description 1
- 101000619542 Homo sapiens E3 ubiquitin-protein ligase parkin Proteins 0.000 description 1
- 101100118549 Homo sapiens EGFR gene Proteins 0.000 description 1
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 1
- 101000998777 Homo sapiens Early placenta insulin-like peptide Proteins 0.000 description 1
- 101000925241 Homo sapiens Ephrin-A3 Proteins 0.000 description 1
- 101001010910 Homo sapiens Estrogen receptor beta Proteins 0.000 description 1
- 101000911074 Homo sapiens FAS-associated death domain protein Proteins 0.000 description 1
- 101000917237 Homo sapiens Fibroblast growth factor 10 Proteins 0.000 description 1
- 101000878124 Homo sapiens Fibroblast growth factor 17 Proteins 0.000 description 1
- 101000846394 Homo sapiens Fibroblast growth factor 19 Proteins 0.000 description 1
- 101000846532 Homo sapiens Fibroblast growth factor 20 Proteins 0.000 description 1
- 101001051973 Homo sapiens Fibroblast growth factor 23 Proteins 0.000 description 1
- 101001060267 Homo sapiens Fibroblast growth factor 5 Proteins 0.000 description 1
- 101001060265 Homo sapiens Fibroblast growth factor 6 Proteins 0.000 description 1
- 101001027382 Homo sapiens Fibroblast growth factor 8 Proteins 0.000 description 1
- 101000738575 Homo sapiens G1/S-specific cyclin-E2 Proteins 0.000 description 1
- 101000822394 Homo sapiens Gamma-aminobutyric acid receptor subunit pi Proteins 0.000 description 1
- 101000997558 Homo sapiens Glutathione hydrolase 1 proenzyme Proteins 0.000 description 1
- 101001082627 Homo sapiens HLA class II histocompatibility antigen gamma chain Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101000872875 Homo sapiens Hepatocyte cell adhesion molecule Proteins 0.000 description 1
- 101000878611 Homo sapiens High affinity immunoglobulin epsilon receptor subunit alpha Proteins 0.000 description 1
- 101000899259 Homo sapiens Histone deacetylase 4 Proteins 0.000 description 1
- 101000899255 Homo sapiens Histone deacetylase 5 Proteins 0.000 description 1
- 101001032113 Homo sapiens Histone deacetylase 7 Proteins 0.000 description 1
- 101001032092 Homo sapiens Histone deacetylase 9 Proteins 0.000 description 1
- 101001019455 Homo sapiens ICOS ligand Proteins 0.000 description 1
- 101000840258 Homo sapiens Immunoglobulin J chain Proteins 0.000 description 1
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 1
- 101001044940 Homo sapiens Insulin-like growth factor-binding protein 2 Proteins 0.000 description 1
- 101001044927 Homo sapiens Insulin-like growth factor-binding protein 3 Proteins 0.000 description 1
- 101000840582 Homo sapiens Insulin-like growth factor-binding protein 6 Proteins 0.000 description 1
- 101001078133 Homo sapiens Integrin alpha-2 Proteins 0.000 description 1
- 101000994378 Homo sapiens Integrin alpha-3 Proteins 0.000 description 1
- 101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 description 1
- 101001046677 Homo sapiens Integrin alpha-V Proteins 0.000 description 1
- 101001015004 Homo sapiens Integrin beta-3 Proteins 0.000 description 1
- 101001015006 Homo sapiens Integrin beta-4 Proteins 0.000 description 1
- 101001054334 Homo sapiens Interferon beta Proteins 0.000 description 1
- 101000599940 Homo sapiens Interferon gamma Proteins 0.000 description 1
- 101001002634 Homo sapiens Interleukin-1 alpha Proteins 0.000 description 1
- 101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 description 1
- 101000994815 Homo sapiens Interleukin-1 receptor accessory protein-like 1 Proteins 0.000 description 1
- 101001076418 Homo sapiens Interleukin-1 receptor type 1 Proteins 0.000 description 1
- 101001076422 Homo sapiens Interleukin-1 receptor type 2 Proteins 0.000 description 1
- 101001083151 Homo sapiens Interleukin-10 receptor subunit alpha Proteins 0.000 description 1
- 101001003149 Homo sapiens Interleukin-10 receptor subunit beta Proteins 0.000 description 1
- 101001003147 Homo sapiens Interleukin-11 receptor subunit alpha Proteins 0.000 description 1
- 101001003138 Homo sapiens Interleukin-12 receptor subunit beta-2 Proteins 0.000 description 1
- 101001003135 Homo sapiens Interleukin-13 receptor subunit alpha-1 Proteins 0.000 description 1
- 101001003132 Homo sapiens Interleukin-13 receptor subunit alpha-2 Proteins 0.000 description 1
- 101001003140 Homo sapiens Interleukin-15 receptor subunit alpha Proteins 0.000 description 1
- 101001019598 Homo sapiens Interleukin-17 receptor A Proteins 0.000 description 1
- 101000998151 Homo sapiens Interleukin-17F Proteins 0.000 description 1
- 101000961065 Homo sapiens Interleukin-18 receptor 1 Proteins 0.000 description 1
- 101001010591 Homo sapiens Interleukin-20 Proteins 0.000 description 1
- 101001010626 Homo sapiens Interleukin-22 Proteins 0.000 description 1
- 101001044883 Homo sapiens Interleukin-22 receptor subunit alpha-1 Proteins 0.000 description 1
- 101001044887 Homo sapiens Interleukin-22 receptor subunit alpha-2 Proteins 0.000 description 1
- 101000853009 Homo sapiens Interleukin-24 Proteins 0.000 description 1
- 101000998140 Homo sapiens Interleukin-36 alpha Proteins 0.000 description 1
- 101000998122 Homo sapiens Interleukin-37 Proteins 0.000 description 1
- 101000599048 Homo sapiens Interleukin-6 receptor subunit alpha Proteins 0.000 description 1
- 101001043809 Homo sapiens Interleukin-7 receptor subunit alpha Proteins 0.000 description 1
- 101001055219 Homo sapiens Interleukin-9 receptor Proteins 0.000 description 1
- 101000605522 Homo sapiens Kallikrein-1 Proteins 0.000 description 1
- 101000605516 Homo sapiens Kallikrein-12 Proteins 0.000 description 1
- 101000605514 Homo sapiens Kallikrein-13 Proteins 0.000 description 1
- 101000605520 Homo sapiens Kallikrein-14 Proteins 0.000 description 1
- 101000605518 Homo sapiens Kallikrein-15 Proteins 0.000 description 1
- 101001091379 Homo sapiens Kallikrein-5 Proteins 0.000 description 1
- 101001091385 Homo sapiens Kallikrein-6 Proteins 0.000 description 1
- 101001091356 Homo sapiens Kallikrein-9 Proteins 0.000 description 1
- 101000998011 Homo sapiens Keratin, type I cytoskeletal 19 Proteins 0.000 description 1
- 101001046960 Homo sapiens Keratin, type II cytoskeletal 1 Proteins 0.000 description 1
- 101001046936 Homo sapiens Keratin, type II cytoskeletal 2 epidermal Proteins 0.000 description 1
- 101001046952 Homo sapiens Keratin, type II cytoskeletal 2 oral Proteins 0.000 description 1
- 101000934753 Homo sapiens Keratin, type II cytoskeletal 75 Proteins 0.000 description 1
- 101001139126 Homo sapiens Krueppel-like factor 6 Proteins 0.000 description 1
- 101000927946 Homo sapiens LisH domain-containing protein ARMC9 Proteins 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 101000739159 Homo sapiens Mammaglobin-A Proteins 0.000 description 1
- 101000739168 Homo sapiens Mammaglobin-B Proteins 0.000 description 1
- 101000990902 Homo sapiens Matrix metalloproteinase-9 Proteins 0.000 description 1
- 101000628547 Homo sapiens Metalloreductase STEAP1 Proteins 0.000 description 1
- 101000628535 Homo sapiens Metalloreductase STEAP2 Proteins 0.000 description 1
- 101000976899 Homo sapiens Mitogen-activated protein kinase 15 Proteins 0.000 description 1
- 101001013159 Homo sapiens Myeloid leukemia factor 2 Proteins 0.000 description 1
- 101000961071 Homo sapiens NF-kappa-B inhibitor alpha Proteins 0.000 description 1
- 101000928278 Homo sapiens Natriuretic peptides B Proteins 0.000 description 1
- 101000995164 Homo sapiens Netrin-4 Proteins 0.000 description 1
- 101000979338 Homo sapiens Nuclear factor NF-kappa-B p100 subunit Proteins 0.000 description 1
- 101000978937 Homo sapiens Nuclear receptor subfamily 0 group B member 2 Proteins 0.000 description 1
- 101000603882 Homo sapiens Nuclear receptor subfamily 1 group I member 3 Proteins 0.000 description 1
- 101000633503 Homo sapiens Nuclear receptor subfamily 2 group E member 1 Proteins 0.000 description 1
- 101001109700 Homo sapiens Nuclear receptor subfamily 4 group A member 1 Proteins 0.000 description 1
- 101001109698 Homo sapiens Nuclear receptor subfamily 4 group A member 2 Proteins 0.000 description 1
- 101001109689 Homo sapiens Nuclear receptor subfamily 4 group A member 3 Proteins 0.000 description 1
- 101001109685 Homo sapiens Nuclear receptor subfamily 5 group A member 2 Proteins 0.000 description 1
- 101001109682 Homo sapiens Nuclear receptor subfamily 6 group A member 1 Proteins 0.000 description 1
- 101001098175 Homo sapiens P2X purinoceptor 7 Proteins 0.000 description 1
- 101000613565 Homo sapiens PRKC apoptosis WT1 regulator protein Proteins 0.000 description 1
- 101001095231 Homo sapiens Peptidyl-prolyl cis-trans isomerase D Proteins 0.000 description 1
- 101000595751 Homo sapiens Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Proteins 0.000 description 1
- 101001091365 Homo sapiens Plasma kallikrein Proteins 0.000 description 1
- 101000582950 Homo sapiens Platelet factor 4 Proteins 0.000 description 1
- 101000613343 Homo sapiens Polycomb group RING finger protein 2 Proteins 0.000 description 1
- 101001056707 Homo sapiens Proepiregulin Proteins 0.000 description 1
- 101000610543 Homo sapiens Prokineticin-2 Proteins 0.000 description 1
- 101000945496 Homo sapiens Proliferation marker protein Ki-67 Proteins 0.000 description 1
- 101001117314 Homo sapiens Prostaglandin D2 receptor 2 Proteins 0.000 description 1
- 101001136592 Homo sapiens Prostate stem cell antigen Proteins 0.000 description 1
- 101000605534 Homo sapiens Prostate-specific antigen Proteins 0.000 description 1
- 101000602015 Homo sapiens Protocadherin gamma-B4 Proteins 0.000 description 1
- 101001110313 Homo sapiens Ras-related C3 botulinum toxin substrate 2 Proteins 0.000 description 1
- 101001132698 Homo sapiens Retinoic acid receptor beta Proteins 0.000 description 1
- 101000650697 Homo sapiens Roundabout homolog 2 Proteins 0.000 description 1
- 101000739195 Homo sapiens Secretoglobin family 1D member 2 Proteins 0.000 description 1
- 101000716809 Homo sapiens Secretogranin-1 Proteins 0.000 description 1
- 101000689224 Homo sapiens Src-like-adapter 2 Proteins 0.000 description 1
- 101000713602 Homo sapiens T-box transcription factor TBX21 Proteins 0.000 description 1
- 101000946860 Homo sapiens T-cell surface glycoprotein CD3 epsilon chain Proteins 0.000 description 1
- 101000738413 Homo sapiens T-cell surface glycoprotein CD3 gamma chain Proteins 0.000 description 1
- 101000738335 Homo sapiens T-cell surface glycoprotein CD3 zeta chain Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 101100425948 Homo sapiens TNFRSF13C gene Proteins 0.000 description 1
- 101000633617 Homo sapiens Thrombospondin-4 Proteins 0.000 description 1
- 101000845170 Homo sapiens Thymic stromal lymphopoietin Proteins 0.000 description 1
- 101000830560 Homo sapiens Toll-interacting protein Proteins 0.000 description 1
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 1
- 101000669460 Homo sapiens Toll-like receptor 5 Proteins 0.000 description 1
- 101000669406 Homo sapiens Toll-like receptor 6 Proteins 0.000 description 1
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 description 1
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 1
- 101000819111 Homo sapiens Trans-acting T-cell-specific transcription factor GATA-3 Proteins 0.000 description 1
- 101000904152 Homo sapiens Transcription factor E2F1 Proteins 0.000 description 1
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 1
- 101000635938 Homo sapiens Transforming growth factor beta-1 proprotein Proteins 0.000 description 1
- 101000851892 Homo sapiens Tropomyosin beta chain Proteins 0.000 description 1
- 101000597779 Homo sapiens Tumor necrosis factor ligand superfamily member 18 Proteins 0.000 description 1
- 101000764263 Homo sapiens Tumor necrosis factor ligand superfamily member 4 Proteins 0.000 description 1
- 101000610604 Homo sapiens Tumor necrosis factor receptor superfamily member 10B Proteins 0.000 description 1
- 101000801254 Homo sapiens Tumor necrosis factor receptor superfamily member 16 Proteins 0.000 description 1
- 101000679921 Homo sapiens Tumor necrosis factor receptor superfamily member 21 Proteins 0.000 description 1
- 101000679857 Homo sapiens Tumor necrosis factor receptor superfamily member 3 Proteins 0.000 description 1
- 101000611185 Homo sapiens Tumor necrosis factor receptor superfamily member 5 Proteins 0.000 description 1
- 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 description 1
- 101000742579 Homo sapiens Vascular endothelial growth factor B Proteins 0.000 description 1
- 101000742596 Homo sapiens Vascular endothelial growth factor C Proteins 0.000 description 1
- 101000742599 Homo sapiens Vascular endothelial growth factor D Proteins 0.000 description 1
- 101001059220 Homo sapiens Zinc finger protein Gfi-1 Proteins 0.000 description 1
- 101000931371 Homo sapiens Zinc finger protein ZFPM2 Proteins 0.000 description 1
- 241000701109 Human adenovirus 2 Species 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 241001354547 Human rhinovirus C3 Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 102100034980 ICOS ligand Human genes 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 108091058536 IL1F9 Proteins 0.000 description 1
- 108700002232 Immediate-Early Genes Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102100029571 Immunoglobulin J chain Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 1
- 102100022710 Insulin-like growth factor-binding protein 2 Human genes 0.000 description 1
- 102100022708 Insulin-like growth factor-binding protein 3 Human genes 0.000 description 1
- 102100029180 Insulin-like growth factor-binding protein 6 Human genes 0.000 description 1
- 102100025305 Integrin alpha-2 Human genes 0.000 description 1
- 102100032819 Integrin alpha-3 Human genes 0.000 description 1
- 102100032816 Integrin alpha-6 Human genes 0.000 description 1
- 102100022339 Integrin alpha-L Human genes 0.000 description 1
- 102100022337 Integrin alpha-V Human genes 0.000 description 1
- 108010041012 Integrin alpha4 Proteins 0.000 description 1
- 102100032999 Integrin beta-3 Human genes 0.000 description 1
- 102100033000 Integrin beta-4 Human genes 0.000 description 1
- 102000008607 Integrin beta3 Human genes 0.000 description 1
- 108010020950 Integrin beta3 Proteins 0.000 description 1
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 1
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 1
- 102100026720 Interferon beta Human genes 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 102100039065 Interleukin-1 beta Human genes 0.000 description 1
- 102100034413 Interleukin-1 receptor accessory protein-like 1 Human genes 0.000 description 1
- 102100026018 Interleukin-1 receptor antagonist protein Human genes 0.000 description 1
- 102100026016 Interleukin-1 receptor type 1 Human genes 0.000 description 1
- 102100026017 Interleukin-1 receptor type 2 Human genes 0.000 description 1
- 102100030236 Interleukin-10 receptor subunit alpha Human genes 0.000 description 1
- 102100020788 Interleukin-10 receptor subunit beta Human genes 0.000 description 1
- 102100020787 Interleukin-11 receptor subunit alpha Human genes 0.000 description 1
- 102100020792 Interleukin-12 receptor subunit beta-2 Human genes 0.000 description 1
- 108010089995 Interleukin-13 Receptor alpha1 Subunit Proteins 0.000 description 1
- 102000008035 Interleukin-13 Receptor alpha1 Subunit Human genes 0.000 description 1
- 108010085418 Interleukin-13 Receptor alpha2 Subunit Proteins 0.000 description 1
- 102000007482 Interleukin-13 Receptor alpha2 Subunit Human genes 0.000 description 1
- 102100020793 Interleukin-13 receptor subunit alpha-2 Human genes 0.000 description 1
- 102100020789 Interleukin-15 receptor subunit alpha Human genes 0.000 description 1
- 102000013691 Interleukin-17 Human genes 0.000 description 1
- 108050003558 Interleukin-17 Proteins 0.000 description 1
- 102100035018 Interleukin-17 receptor A Human genes 0.000 description 1
- 102100033454 Interleukin-17F Human genes 0.000 description 1
- 102100039340 Interleukin-18 receptor 1 Human genes 0.000 description 1
- 108050009288 Interleukin-19 Proteins 0.000 description 1
- 108010082786 Interleukin-1alpha Proteins 0.000 description 1
- 102100030692 Interleukin-20 Human genes 0.000 description 1
- 102100030703 Interleukin-22 Human genes 0.000 description 1
- 102100022723 Interleukin-22 receptor subunit alpha-1 Human genes 0.000 description 1
- 102100022703 Interleukin-22 receptor subunit alpha-2 Human genes 0.000 description 1
- 102000013264 Interleukin-23 Human genes 0.000 description 1
- 102100036671 Interleukin-24 Human genes 0.000 description 1
- 102100033474 Interleukin-36 alpha Human genes 0.000 description 1
- 102100033503 Interleukin-36 gamma Human genes 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 102100021592 Interleukin-7 Human genes 0.000 description 1
- 102100021593 Interleukin-7 receptor subunit alpha Human genes 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- 102100038318 Kallikrein-12 Human genes 0.000 description 1
- 102100038315 Kallikrein-13 Human genes 0.000 description 1
- 102100038298 Kallikrein-14 Human genes 0.000 description 1
- 102100038301 Kallikrein-15 Human genes 0.000 description 1
- 102100034872 Kallikrein-4 Human genes 0.000 description 1
- 102100034868 Kallikrein-5 Human genes 0.000 description 1
- 102100034866 Kallikrein-6 Human genes 0.000 description 1
- 102100034876 Kallikrein-9 Human genes 0.000 description 1
- 102100022905 Keratin, type II cytoskeletal 1 Human genes 0.000 description 1
- 102100022854 Keratin, type II cytoskeletal 2 epidermal Human genes 0.000 description 1
- 102100022926 Keratin, type II cytoskeletal 2 oral Human genes 0.000 description 1
- 102100025367 Keratin, type II cytoskeletal 75 Human genes 0.000 description 1
- 108010066302 Keratin-19 Proteins 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 102100020679 Krueppel-like factor 6 Human genes 0.000 description 1
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000282838 Lama Species 0.000 description 1
- 235000019687 Lamb Nutrition 0.000 description 1
- 102100038269 Large neutral amino acids transporter small subunit 3 Human genes 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 102100036882 LisH domain-containing protein ARMC9 Human genes 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- 101710172064 Low-density lipoprotein receptor-related protein Proteins 0.000 description 1
- 102100040705 Low-density lipoprotein receptor-related protein 8 Human genes 0.000 description 1
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000007993 MOPS buffer Substances 0.000 description 1
- 101150053046 MYD88 gene Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 108010031030 Mammaglobin A Proteins 0.000 description 1
- 108010031029 Mammaglobin B Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 108090000301 Membrane transport proteins Proteins 0.000 description 1
- 102000003939 Membrane transport proteins Human genes 0.000 description 1
- 102100026712 Metalloreductase STEAP1 Human genes 0.000 description 1
- 102100026711 Metalloreductase STEAP2 Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108010092801 Midkine Proteins 0.000 description 1
- 101710151803 Mitochondrial intermediate peptidase 2 Proteins 0.000 description 1
- 102100023483 Mitogen-activated protein kinase 15 Human genes 0.000 description 1
- 101100481406 Mus musculus Tie1 gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102100026784 Myelin proteolipid protein Human genes 0.000 description 1
- 101710094913 Myelin proteolipid protein Proteins 0.000 description 1
- 102100024134 Myeloid differentiation primary response protein MyD88 Human genes 0.000 description 1
- 102100029687 Myeloid leukemia factor 2 Human genes 0.000 description 1
- 102100031789 Myeloid-derived growth factor Human genes 0.000 description 1
- 102100039337 NF-kappa-B inhibitor alpha Human genes 0.000 description 1
- 102100036836 Natriuretic peptides B Human genes 0.000 description 1
- 108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 1
- 108010043296 Neurocan Proteins 0.000 description 1
- 102100030466 Neurocan core protein Human genes 0.000 description 1
- 108090000770 Neuropilin-2 Proteins 0.000 description 1
- 101100407828 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) ptr-3 gene Proteins 0.000 description 1
- 108010077641 Nogo Proteins Proteins 0.000 description 1
- 102000010410 Nogo Proteins Human genes 0.000 description 1
- 108091060545 Nonsense suppressor Proteins 0.000 description 1
- 102100023059 Nuclear factor NF-kappa-B p100 subunit Human genes 0.000 description 1
- 102100023172 Nuclear receptor subfamily 0 group B member 2 Human genes 0.000 description 1
- 102100023171 Nuclear receptor subfamily 1 group D member 2 Human genes 0.000 description 1
- 102100038494 Nuclear receptor subfamily 1 group I member 2 Human genes 0.000 description 1
- 102100038512 Nuclear receptor subfamily 1 group I member 3 Human genes 0.000 description 1
- 102100028470 Nuclear receptor subfamily 2 group C member 1 Human genes 0.000 description 1
- 102100029534 Nuclear receptor subfamily 2 group E member 1 Human genes 0.000 description 1
- 102100022679 Nuclear receptor subfamily 4 group A member 1 Human genes 0.000 description 1
- 102100022676 Nuclear receptor subfamily 4 group A member 2 Human genes 0.000 description 1
- 102100022673 Nuclear receptor subfamily 4 group A member 3 Human genes 0.000 description 1
- 102100022669 Nuclear receptor subfamily 5 group A member 2 Human genes 0.000 description 1
- 102100022670 Nuclear receptor subfamily 6 group A member 1 Human genes 0.000 description 1
- 108010079246 OMPA outer membrane proteins Proteins 0.000 description 1
- 108010042215 OX40 Ligand Proteins 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 102100021079 Ornithine decarboxylase Human genes 0.000 description 1
- 108700005126 Ornithine decarboxylases Proteins 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102100037602 P2X purinoceptor 7 Human genes 0.000 description 1
- 108091033411 PCA3 Proteins 0.000 description 1
- 102100040853 PRKC apoptosis WT1 regulator protein Human genes 0.000 description 1
- 101150084398 PTAFR gene Proteins 0.000 description 1
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 1
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 1
- 101710124046 Palmitoyl-acyl carrier protein thioesterase, chloroplastic Proteins 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 108010087702 Penicillinase Proteins 0.000 description 1
- 102100037827 Peptidyl-prolyl cis-trans isomerase D Human genes 0.000 description 1
- 102100036052 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Human genes 0.000 description 1
- 108090000316 Pitrilysin Proteins 0.000 description 1
- 102100034869 Plasma kallikrein Human genes 0.000 description 1
- 102100030304 Platelet factor 4 Human genes 0.000 description 1
- 108700023400 Platelet-activating factor receptors Proteins 0.000 description 1
- 102100037596 Platelet-derived growth factor subunit A Human genes 0.000 description 1
- 102100040990 Platelet-derived growth factor subunit B Human genes 0.000 description 1
- 102100030477 Plectin Human genes 0.000 description 1
- 108010054050 Plectin Proteins 0.000 description 1
- 229920000805 Polyaspartic acid Polymers 0.000 description 1
- 102100040919 Polycomb group RING finger protein 2 Human genes 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- 108010001511 Pregnane X Receptor Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102100033237 Pro-epidermal growth factor Human genes 0.000 description 1
- 241000677647 Proba Species 0.000 description 1
- 102100025498 Proepiregulin Human genes 0.000 description 1
- 102100040125 Prokineticin-2 Human genes 0.000 description 1
- 102100036691 Proliferating cell nuclear antigen Human genes 0.000 description 1
- 102100034836 Proliferation marker protein Ki-67 Human genes 0.000 description 1
- 102100024218 Prostaglandin D2 receptor 2 Human genes 0.000 description 1
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 1
- 102100036735 Prostate stem cell antigen Human genes 0.000 description 1
- 101710127332 Protease I Proteins 0.000 description 1
- 101800004937 Protein C Proteins 0.000 description 1
- 108010015499 Protein Kinase C-theta Proteins 0.000 description 1
- 108010001267 Protein Subunits Proteins 0.000 description 1
- 102000002067 Protein Subunits Human genes 0.000 description 1
- 102100021566 Protein kinase C theta type Human genes 0.000 description 1
- 102100034433 Protein kinase C-binding protein NELL2 Human genes 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 108010019674 Proto-Oncogene Proteins c-sis Proteins 0.000 description 1
- 101100084022 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) lapA gene Proteins 0.000 description 1
- 108010007100 Pulmonary Surfactant-Associated Protein A Proteins 0.000 description 1
- 102100027773 Pulmonary surfactant-associated protein A2 Human genes 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 102100022129 Ras-related C3 botulinum toxin substrate 2 Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 1
- 102100033909 Retinoic acid receptor beta Human genes 0.000 description 1
- 108091008770 Rev-ErbAß Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 102100027739 Roundabout homolog 2 Human genes 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 108010005173 SERPIN-B5 Proteins 0.000 description 1
- 108091006299 SLC2A2 Proteins 0.000 description 1
- 108091006570 SLC33A1 Proteins 0.000 description 1
- 108091006993 SLC43A1 Proteins 0.000 description 1
- 108010011005 STAT6 Transcription Factor Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 1
- 102100036546 Salivary acidic proline-rich phosphoprotein 1/2 Human genes 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 101800001700 Saposin-D Proteins 0.000 description 1
- 102100037279 Secretoglobin family 1D member 2 Human genes 0.000 description 1
- 102100020867 Secretogranin-1 Human genes 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 102100030333 Serpin B5 Human genes 0.000 description 1
- 108010089417 Sex Hormone-Binding Globulin Proteins 0.000 description 1
- 102100030758 Sex hormone-binding globulin Human genes 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- 102100023980 Signal transducer and activator of transcription 6 Human genes 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 241000256248 Spodoptera Species 0.000 description 1
- 241000256251 Spodoptera frugiperda Species 0.000 description 1
- 102100024510 Src-like-adapter 2 Human genes 0.000 description 1
- 108010088160 Staphylococcal Protein A Proteins 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 108010048349 Steroidogenic Factor 1 Proteins 0.000 description 1
- 102100029856 Steroidogenic factor 1 Human genes 0.000 description 1
- 102100036840 T-box transcription factor TBX21 Human genes 0.000 description 1
- 102100035794 T-cell surface glycoprotein CD3 epsilon chain Human genes 0.000 description 1
- 102100037911 T-cell surface glycoprotein CD3 gamma chain Human genes 0.000 description 1
- 102100037906 T-cell surface glycoprotein CD3 zeta chain Human genes 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 102100033455 TGF-beta receptor type-2 Human genes 0.000 description 1
- 108090000925 TNF receptor-associated factor 2 Proteins 0.000 description 1
- 102000004399 TNF receptor-associated factor 3 Human genes 0.000 description 1
- 108090000922 TNF receptor-associated factor 3 Proteins 0.000 description 1
- 102000003715 TNF receptor-associated factor 4 Human genes 0.000 description 1
- 108090000008 TNF receptor-associated factor 4 Proteins 0.000 description 1
- 102000003718 TNF receptor-associated factor 5 Human genes 0.000 description 1
- 108090000001 TNF receptor-associated factor 5 Proteins 0.000 description 1
- 102000003714 TNF receptor-associated factor 6 Human genes 0.000 description 1
- 108090000009 TNF receptor-associated factor 6 Proteins 0.000 description 1
- 102100034779 TRAF family member-associated NF-kappa-B activator Human genes 0.000 description 1
- 102000003623 TRPC6 Human genes 0.000 description 1
- 101710137710 Thioesterase 1/protease 1/lysophospholipase L1 Proteins 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 102100029219 Thrombospondin-4 Human genes 0.000 description 1
- 102100031294 Thymic stromal lymphopoietin Human genes 0.000 description 1
- 241000723792 Tobacco etch virus Species 0.000 description 1
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 1
- 102100024652 Toll-interacting protein Human genes 0.000 description 1
- 102000002689 Toll-like receptor Human genes 0.000 description 1
- 108020000411 Toll-like receptor Proteins 0.000 description 1
- 102100024324 Toll-like receptor 3 Human genes 0.000 description 1
- 102100039357 Toll-like receptor 5 Human genes 0.000 description 1
- 102100039387 Toll-like receptor 6 Human genes 0.000 description 1
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 1
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 1
- 102100033117 Toll-like receptor 9 Human genes 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- 102100021386 Trans-acting T-cell-specific transcription factor GATA-3 Human genes 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 102100024026 Transcription factor E2F1 Human genes 0.000 description 1
- 102100023132 Transcription factor Jun Human genes 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 108010033576 Transferrin Receptors Proteins 0.000 description 1
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 1
- 108010082684 Transforming Growth Factor-beta Type II Receptor Proteins 0.000 description 1
- 102100030742 Transforming growth factor beta-1 proprotein Human genes 0.000 description 1
- 108050001421 Transient receptor potential channel, canonical 6 Proteins 0.000 description 1
- 102100036471 Tropomyosin beta chain Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 1
- 102100035283 Tumor necrosis factor ligand superfamily member 18 Human genes 0.000 description 1
- 102100040112 Tumor necrosis factor receptor superfamily member 10B Human genes 0.000 description 1
- 102100029690 Tumor necrosis factor receptor superfamily member 13C Human genes 0.000 description 1
- 102100022156 Tumor necrosis factor receptor superfamily member 3 Human genes 0.000 description 1
- 102100040403 Tumor necrosis factor receptor superfamily member 6 Human genes 0.000 description 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 1
- 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 244000000188 Vaccinium ovalifolium Species 0.000 description 1
- 108010073919 Vascular Endothelial Growth Factor D Proteins 0.000 description 1
- 102100038217 Vascular endothelial growth factor B Human genes 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 102100029004 Zinc finger protein Gfi-1 Human genes 0.000 description 1
- 102100020996 Zinc finger protein ZFPM2 Human genes 0.000 description 1
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
- SNEIUMQYRCDYCH-UHFFFAOYSA-N acetylarginine Chemical compound CC(=O)NC(C(O)=O)CCCN=C(N)N SNEIUMQYRCDYCH-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
- 108090000185 alpha-Synuclein Proteins 0.000 description 1
- 229940126574 aminoglycoside antibiotic Drugs 0.000 description 1
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 238000011091 antibody purification Methods 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 238000012219 cassette mutagenesis Methods 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- HJWLJNBZVZDLAQ-HAQNSBGRSA-N chembl2103874 Chemical compound C1C[C@@H](CS(=O)(=O)NC)CC[C@@H]1N(C)C1=NC=NC2=C1C=CN2 HJWLJNBZVZDLAQ-HAQNSBGRSA-N 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 230000001447 compensatory effect Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 239000005289 controlled pore glass Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- VHJLVAABSRFDPM-ZXZARUISSA-N dithioerythritol Chemical compound SC[C@H](O)[C@H](O)CS VHJLVAABSRFDPM-ZXZARUISSA-N 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000001983 electron spin resonance imaging Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 229940066758 endopeptidases Drugs 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 239000006167 equilibration buffer Substances 0.000 description 1
- 235000020774 essential nutrients Nutrition 0.000 description 1
- 108090000047 fibroblast growth factor 13 Proteins 0.000 description 1
- 102000003684 fibroblast growth factor 13 Human genes 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Natural products O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 1
- 102000018146 globin Human genes 0.000 description 1
- 108060003196 globin Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 210000005256 gram-negative cell Anatomy 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000012872 hydroxylapatite chromatography Methods 0.000 description 1
- 101150020087 ilvG gene Proteins 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000014726 immortalization of host cell Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 229910052816 inorganic phosphate Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 108010021315 integrin beta7 Proteins 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 102000004114 interleukin 20 Human genes 0.000 description 1
- 108090000681 interleukin 20 Proteins 0.000 description 1
- 102000014909 interleukin-1 receptor activity proteins Human genes 0.000 description 1
- 108040006732 interleukin-1 receptor activity proteins Proteins 0.000 description 1
- 108040002014 interleukin-18 receptor activity proteins Proteins 0.000 description 1
- 102000008625 interleukin-18 receptor activity proteins Human genes 0.000 description 1
- 108040006852 interleukin-4 receptor activity proteins Proteins 0.000 description 1
- 108040006859 interleukin-5 receptor activity proteins Proteins 0.000 description 1
- 108040006858 interleukin-6 receptor activity proteins Proteins 0.000 description 1
- 108040006862 interleukin-9 receptor activity proteins Proteins 0.000 description 1
- 108010024383 kallikrein 4 Proteins 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 229940039088 kininogenase Drugs 0.000 description 1
- 101150109249 lacI gene Proteins 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 235000015250 liver sausages Nutrition 0.000 description 1
- 108010031117 low density lipoprotein receptor-related protein 8 Proteins 0.000 description 1
- 101150074251 lpp gene Proteins 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000009061 membrane transport Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000033116 oxidation-reduction process Effects 0.000 description 1
- 102000045222 parkin Human genes 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229950009506 penicillinase Drugs 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 101150009573 phoA gene Proteins 0.000 description 1
- 238000005375 photometry Methods 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 102000030769 platelet activating factor receptor Human genes 0.000 description 1
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 1
- 229920006112 polar polymer Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 108010064470 polyaspartate Proteins 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 108010043383 protease V Proteins 0.000 description 1
- 229960000856 protein c Drugs 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000010405 reoxidation reaction Methods 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- XYSQXZCMOLNHOI-UHFFFAOYSA-N s-[2-[[4-(acetylsulfamoyl)phenyl]carbamoyl]phenyl] 5-pyridin-1-ium-1-ylpentanethioate;bromide Chemical compound [Br-].C1=CC(S(=O)(=O)NC(=O)C)=CC=C1NC(=O)C1=CC=CC=C1SC(=O)CCCC[N+]1=CC=CC=C1 XYSQXZCMOLNHOI-UHFFFAOYSA-N 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000011218 seed culture Methods 0.000 description 1
- 210000000717 sertoli cell Anatomy 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 108091008744 testicular receptors 2 Proteins 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940071127 thioglycolate Drugs 0.000 description 1
- CWERGRDVMFNCDR-UHFFFAOYSA-M thioglycolate(1-) Chemical compound [O-]C(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-M 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 238000011426 transformation method Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 101150057627 trxB gene Proteins 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229960001322 trypsin Drugs 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/36—Extraction; Separation; Purification by a combination of two or more processes of different types
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/70—Vectors or expression systems specially adapted for E. coli
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/522—CH1 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/524—CH2 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/526—CH3 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/53—Hinge
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161545863P | 2011-10-11 | 2011-10-11 | |
| US61/545,863 | 2011-10-11 | ||
| US201161546503P | 2011-10-12 | 2011-10-12 | |
| US61/546,503 | 2011-10-12 | ||
| US201161560704P | 2011-11-16 | 2011-11-16 | |
| US61/560,704 | 2011-11-16 | ||
| US201261676837P | 2012-07-27 | 2012-07-27 | |
| US61/676,837 | 2012-07-27 | ||
| PCT/US2012/059810 WO2013055958A1 (en) | 2011-10-11 | 2012-10-11 | Improved assembly of bispecific antibodies |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014534198A JP2014534198A (ja) | 2014-12-18 |
| JP2014534198A5 JP2014534198A5 (ru) | 2015-12-03 |
| JP6216321B2 true JP6216321B2 (ja) | 2017-10-18 |
Family
ID=47073551
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014535885A Active JP6216321B2 (ja) | 2011-10-11 | 2012-10-11 | 二重特異性抗体の構築の改善 |
Country Status (17)
| Country | Link |
|---|---|
| US (4) | US9862778B2 (ru) |
| EP (2) | EP2766397B1 (ru) |
| JP (1) | JP6216321B2 (ru) |
| KR (3) | KR102219217B1 (ru) |
| CN (2) | CN104093744A (ru) |
| BR (1) | BR112014008684B1 (ru) |
| CA (1) | CA2850818A1 (ru) |
| ES (2) | ES2971444T3 (ru) |
| HK (2) | HK1200844A1 (ru) |
| HR (2) | HRP20240230T1 (ru) |
| HU (1) | HUE065876T2 (ru) |
| MX (1) | MX359384B (ru) |
| PL (2) | PL2766397T3 (ru) |
| RU (1) | RU2654567C2 (ru) |
| SI (1) | SI2766397T1 (ru) |
| TR (1) | TR201809151T4 (ru) |
| WO (1) | WO2013055958A1 (ru) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2850818A1 (en) * | 2011-10-11 | 2013-04-18 | Genentech, Inc. | Improved assembly of bispecific antibodies |
| WO2014122144A1 (en) | 2013-02-05 | 2014-08-14 | Engmab Ag | BISPECIFIC ANTIBODIES AGAINST CD3ε AND BCMA |
| ES2676023T3 (es) | 2013-03-15 | 2018-07-16 | F. Hoffmann-La Roche Ag | Polipéptidos de IL-22 y proteínas de fusión de IL-22 Fc y métodos de uso |
| WO2014189306A1 (ko) * | 2013-05-22 | 2014-11-27 | 메타볼랩(주) | 항 ＴＮＦ-α/ＣＸＣＬ10 이중 타겟 항체 및 그의 용도 |
| US10370776B2 (en) * | 2013-09-25 | 2019-08-06 | Idea Orchard, Llc | Antibody like protein |
| AU2014357292B2 (en) | 2013-11-27 | 2020-06-25 | Zymeworks Bc Inc. | Bispecific antigen-binding constructs targeting HER2 |
| UA117608C2 (uk) | 2014-02-21 | 2018-08-27 | Дженентек, Інк. | Спосіб лікування еозинофільного захворювання у пацієнта шляхом застосування біспецифічного анти-il-13/il-17 антитіла |
| CN106471117A (zh) * | 2014-05-06 | 2017-03-01 | 豪夫迈·罗氏有限公司 | 使用哺乳动物细胞产生异多聚体蛋白 |
| US10647777B2 (en) * | 2014-05-28 | 2020-05-12 | Genzyme Corporation | Methods of controlling the formation of disulfide bonds in protein solutions |
| CN104195173B (zh) * | 2014-09-02 | 2017-03-08 | 北京比洋生物技术有限公司 | 具有双表达盒的谷氨酰胺合成酶高效表达载体 |
| CA2966558C (en) | 2014-11-05 | 2024-03-12 | Genentech, Inc. | Methods of producing two chain proteins in bacteria |
| AU2015342964B2 (en) | 2014-11-05 | 2021-06-24 | Genentech, Inc. | Methods of producing two chain proteins in bacteria |
| WO2016082044A1 (en) * | 2014-11-27 | 2016-06-02 | Zymeworks Inc. | Methods of using bispecific antigen-binding constructs targeting her2 |
| AU2016232349B2 (en) * | 2015-03-13 | 2022-01-20 | Novimmune Sa | Methods of purifying bispecific antibodies |
| GB201506869D0 (en) | 2015-04-22 | 2015-06-03 | Ucb Biopharma Sprl | Method |
| AU2016312259B2 (en) | 2015-08-26 | 2018-12-06 | Bison Therapeutics Inc. | Multispecific antibody platform and related methods |
| JP6998869B2 (ja) | 2015-11-08 | 2022-02-04 | ジェネンテック， インコーポレイテッド | 多重特異性抗体のスクリーニング方法 |
| EP3472177B1 (en) | 2016-06-17 | 2024-08-14 | F. Hoffmann-La Roche AG | Purification of multispecific antibodies |
| US11510871B2 (en) | 2016-09-16 | 2022-11-29 | Leukocare Ag | Method for producing low viscous and highly concentrated biopharmaceutical drug products in liquid formulation |
| RU2744630C2 (ru) * | 2016-09-16 | 2021-03-12 | Льюкокэар Аг | Новый способ стабилизации биофармацевтического лекарственного продукта при производстве |
| US20230192896A1 (en) | 2016-11-23 | 2023-06-22 | Bioverativ Therapeutics Inc. | Bispecific antibodies binding to coagulation factor ix and coagulation factor x |
| EP3586872A4 (en) * | 2017-02-24 | 2020-12-30 | Chugai Seiyaku Kabushiki Kaisha | PHARMACEUTICAL COMPOSITION, ANTIG-BINDING MOLECULES, TREATMENT METHODS AND SCREENING METHODS |
| JOP20190248A1 (ar) | 2017-04-21 | 2019-10-20 | Amgen Inc | بروتينات ربط مولد ضد trem2 واستخداماته |
| SG11201909728XA (en) | 2017-04-26 | 2019-11-28 | Eureka Therapeutics Inc | Constructs specifically recognizing glypican 3 and uses thereof |
| US20180344869A1 (en) * | 2017-05-18 | 2018-12-06 | Hoffmann-La Roche Inc. | Reduction of application-related side reaction of a therapeutic antibody |
| US11952422B2 (en) | 2017-12-05 | 2024-04-09 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule comprising altered antibody variable region binding CD3 and CD137 |
| KR20210056288A (ko) | 2018-06-01 | 2021-05-18 | 타유 후아시아 바이오테크 메디컬 그룹 컴퍼니 리미티드 | 질환 또는 병태를 치료하기 위한 조성물 및 그의 용도 |
| AU2019280900A1 (en) | 2018-06-09 | 2020-11-19 | Boehringer Ingelheim International Gmbh | DLL3-CD3 bispecific antibodies |
| CA3112655A1 (en) * | 2018-10-01 | 2020-04-09 | Amgen Inc. | Methods for reducing aggregation of bispecific antibodies |
| CN113508135A (zh) | 2018-10-29 | 2021-10-15 | 比奥根Ma公司 | 增强血脑屏障转运的人源化和稳定化的fc5变体 |
| EP3877407A1 (en) | 2018-11-05 | 2021-09-15 | F. Hoffmann-La Roche AG | Methods of producing two chain proteins in prokaryotic host cells |
| JOP20210233A1 (ar) | 2019-02-26 | 2023-01-30 | Janssen Biotech Inc | علاجات مركبة وتطابق المريض مع الأجسام ثنائية النوعية المضادة لـ EGFR/c-Met. |
| KR20220005031A (ko) * | 2019-04-25 | 2022-01-12 | 에프. 호프만-라 로슈 아게 | 폴리펩티드 사슬 교환에 의한 항체-유래된 폴리펩티드의 산출 |
| JOP20210304A1 (ar) | 2019-05-14 | 2023-01-30 | Janssen Biotech Inc | علاجات مركبة باستخدام الأجسام المضادة ثنائية النوعية المضادة لمستقبل عامل نمو البشرة (EGFR)/ مستقبل عامل نمو خلايا الكبد (c-Met) ومثبطات كيناز التيروسين الخاصة بمستقبل عامل نمو البشرة (EGFR) من الجيل الثالث |
| GB2599546A (en) * | 2019-05-31 | 2022-04-06 | Univ Johns Hopkins | IL-ER#/IL-8R Bispecific binding agents for inhibiting cancer cell migration |
| GB2599814A (en) * | 2019-05-31 | 2022-04-13 | Univ Johns Hopkins | Bispecific binding agents |
| KR20220113353A (ko) | 2019-09-18 | 2022-08-12 | 람캅 바이오 알파 에이지 | Ceacam5 및 cd3에 대한 이중특이적 항체 |
| CA3173519A1 (en) * | 2020-03-31 | 2021-10-07 | Vishnu Priyanka Reddy CHICHILI | Method for producing multispecific antigen-binding molecules |
| EP4126969A4 (en) | 2020-03-31 | 2024-05-29 | Chugai Seiyaku Kabushiki Kaisha | MULTISPECIFIC ANTIGEN-BINDING MOLECULES TARGETING DLL3 AND THEIR USES |
| CN111748527B (zh) * | 2020-05-15 | 2021-01-29 | 上海多宁生物科技有限公司 | 化学成分限定高效补料培养基及其制备方法和应用 |
| AU2021362007A1 (en) | 2020-10-16 | 2023-06-22 | Invisishield Technologies Ltd. | Compositions for preventing or treating viral and other microbial infections |
| CN114539417A (zh) * | 2020-11-26 | 2022-05-27 | 盛禾(中国)生物制药有限公司 | 一种有效去除双特异性抗体同源二聚体的层析纯化工艺 |
| AU2021395729A1 (en) | 2020-12-07 | 2023-07-13 | UCB Biopharma SRL | Multi-specific antibodies and antibody combinations |
Family Cites Families (71)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE30985E (en) | 1978-01-01 | 1982-06-29 | Serum-free cell culture media | |
| US4419446A (en) | 1980-12-31 | 1983-12-06 | The United States Of America As Represented By The Department Of Health And Human Services | Recombinant DNA process utilizing a papilloma virus DNA as a vector |
| US4444878A (en) * | 1981-12-21 | 1984-04-24 | Boston Biomedical Research Institute, Inc. | Bispecific antibody determinants |
| US5292668A (en) | 1981-12-21 | 1994-03-08 | Boston Biomedical Research Institute, Inc. | Bispecific antibody determinants |
| US4601978A (en) | 1982-11-24 | 1986-07-22 | The Regents Of The University Of California | Mammalian metallothionein promoter system |
| US4560655A (en) | 1982-12-16 | 1985-12-24 | Immunex Corporation | Serum-free cell culture medium and process for making same |
| US4657866A (en) | 1982-12-21 | 1987-04-14 | Sudhir Kumar | Serum-free, synthetic, completely chemically defined tissue culture media |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4767704A (en) | 1983-10-07 | 1988-08-30 | Columbia University In The City Of New York | Protein-free culture medium |
| US4965199A (en) | 1984-04-20 | 1990-10-23 | Genentech, Inc. | Preparation of functional human factor VIII in mammalian cells using methotrexate based selection |
| GB8516415D0 (en) | 1985-06-28 | 1985-07-31 | Celltech Ltd | Culture of animal cells |
| SE8505922D0 (sv) | 1985-12-13 | 1985-12-13 | Kabigen Ab | Construction of an igg binding protein to facilitate downstream processing using protein engineering |
| US4927762A (en) | 1986-04-01 | 1990-05-22 | Cell Enterprises, Inc. | Cell culture medium with antioxidant |
| JP2665353B2 (ja) * | 1988-09-10 | 1997-10-22 | 住商ファーマインターナショナル株式会社 | 双特異性抗体の製造法 |
| WO1990003430A1 (en) | 1988-09-23 | 1990-04-05 | Cetus Corporation | Cell culture medium for enhanced cell growth, culture longevity and product expression |
| DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
| US5122469A (en) | 1990-10-03 | 1992-06-16 | Genentech, Inc. | Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins |
| US5508192A (en) | 1990-11-09 | 1996-04-16 | Board Of Regents, The University Of Texas System | Bacterial host strains for producing proteolytically sensitive polypeptides |
| US5264365A (en) | 1990-11-09 | 1993-11-23 | Board Of Regents, The University Of Texas System | Protease-deficient bacterial strains for production of proteolytically sensitive polypeptides |
| US7018809B1 (en) | 1991-09-19 | 2006-03-28 | Genentech, Inc. | Expression of functional antibody fragments |
| EP1136556B1 (en) | 1991-11-25 | 2005-06-08 | Enzon, Inc. | Method of producing multivalent antigen-binding proteins |
| NZ258392A (en) | 1992-11-13 | 1997-09-22 | Idec Pharma Corp | Chimeric and radiolabelled antibodies to the b lymphocyte cellsurface antigen bp35 (cd-20) and their use in the treatment of b cell lymphona |
| UA40577C2 (ru) * | 1993-08-02 | 2001-08-15 | Мерк Патент Гмбх | Биспецифическая молекула, которая используется для лизиса опухолевых клеток, способ ее получения, моноклональное антитело (варианты), фармацевтический препарат, фармацевтический набор (варианты), способ удаления опухолевых клеток |
| SE9400088D0 (sv) | 1994-01-14 | 1994-01-14 | Kabi Pharmacia Ab | Bacterial receptor structures |
| US5789229A (en) | 1994-09-30 | 1998-08-04 | Uab Research Foundation | Stranded RNA virus particles |
| US5639635A (en) | 1994-11-03 | 1997-06-17 | Genentech, Inc. | Process for bacterial production of polypeptides |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| US5641870A (en) | 1995-04-20 | 1997-06-24 | Genentech, Inc. | Low pH hydrophobic interaction chromatography for antibody purification |
| AU2660397A (en) | 1996-04-05 | 1997-10-29 | Board Of Regents, The University Of Texas System | Methods for producing soluble, biologically-active disulfide bond-containing eukaryotic proteins in bacterial cells |
| US20020062010A1 (en) | 1997-05-02 | 2002-05-23 | Genentech, Inc. | Method for making multispecific antibodies having heteromultimeric and common components |
| EP0979281B1 (en) | 1997-05-02 | 2005-07-20 | Genentech, Inc. | A method for making multispecific antibodies having heteromultimeric and common components |
| US6083715A (en) | 1997-06-09 | 2000-07-04 | Board Of Regents, The University Of Texas System | Methods for producing heterologous disulfide bond-containing polypeptides in bacterial cells |
| AU773891C (en) | 1998-10-23 | 2005-02-17 | Kirin-Amgen Inc. | Dimeric thrombopoietin peptide mimetics binding to MP1 receptor and having thrombopoietic activity |
| US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| IL127127A0 (en) | 1998-11-18 | 1999-09-22 | Peptor Ltd | Small functional units of antibody heavy chain variable regions |
| KR20020093029A (ko) | 2000-04-11 | 2002-12-12 | 제넨테크, 인크. | 다가 항체 및 그의 용도 |
| US8372954B2 (en) | 2000-12-22 | 2013-02-12 | National Research Council Of Canada | Phage display libraries of human VH fragments |
| DK1385882T3 (da) | 2001-05-11 | 2008-02-11 | Amgen Inc | Peptider og relaterede molekyler, der binder til TALL-1 |
| US7332474B2 (en) | 2001-10-11 | 2008-02-19 | Amgen Inc. | Peptides and related compounds having thrombopoietic activity |
| US7138370B2 (en) | 2001-10-11 | 2006-11-21 | Amgen Inc. | Specific binding agents of human angiopoietin-2 |
| US7205275B2 (en) | 2001-10-11 | 2007-04-17 | Amgen Inc. | Methods of treatment using specific binding agents of human angiopoietin-2 |
| JP2005289809A (ja) | 2001-10-24 | 2005-10-20 | Vlaams Interuniversitair Inst Voor Biotechnologie Vzw (Vib Vzw) | 突然変異重鎖抗体 |
| US6731168B2 (en) * | 2002-02-06 | 2004-05-04 | Intersil Americas, Inc. | Power amplifier linearizer that compensates for long-time-constant memory effects and method therefor |
| PT1523496E (pt) | 2002-07-18 | 2011-09-29 | Merus B V | Produção de misturas de anticorpos de forma recombinante |
| CN1268761C (zh) * | 2002-08-29 | 2006-08-09 | 上海凯曼生物科技有限公司 | 一种制备人载脂蛋白基因重组蛋白的方法 |
| US6919426B2 (en) | 2002-09-19 | 2005-07-19 | Amgen Inc. | Peptides and related molecules that modulate nerve growth factor activity |
| WO2004055164A2 (en) * | 2002-12-13 | 2004-07-01 | Abgenix, Inc. | System and method for stabilizing antibodies with histidine |
| DK1581644T3 (da) | 2003-01-09 | 2007-10-08 | Genentech Inc | Oprensning af polypeptider |
| AU2004229335C1 (en) | 2003-04-04 | 2010-06-17 | Genentech, Inc. | High concentration antibody and protein formulations |
| ES2315664T3 (es) | 2003-06-30 | 2009-04-01 | Domantis Limited | Anticuerpos de dominio unico (dab) pegilados. |
| KR101247908B1 (ko) | 2004-09-02 | 2013-03-26 | 제넨테크, 인크. | 항-ｆｃ-감마 ｒｉｉｂ 수용체 항체 및 그의 용도 |
| US20060204493A1 (en) * | 2004-09-02 | 2006-09-14 | Genentech, Inc. | Heteromultimeric molecules |
| US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
| US20070274985A1 (en) * | 2006-05-26 | 2007-11-29 | Stefan Dubel | Antibody |
| US20090182127A1 (en) | 2006-06-22 | 2009-07-16 | Novo Nordisk A/S | Production of Bispecific Antibodies |
| US8557446B2 (en) | 2006-08-14 | 2013-10-15 | Enerize Corporation | Proton-conducting polyamide polymer membrane and method for production |
| WO2008031020A2 (en) | 2006-09-08 | 2008-03-13 | Wyeth | Arginine wash in protein purification using affinity chromatography |
| CN104497143B (zh) * | 2007-03-29 | 2020-08-25 | 健玛保 | 双特异性抗体及其制造方法 |
| US20090252729A1 (en) * | 2007-05-14 | 2009-10-08 | Farrington Graham K | Single-chain Fc (scFc) regions, binding polypeptides comprising same, and methods related thereto |
| WO2008145142A1 (en) | 2007-05-31 | 2008-12-04 | Genmab A/S | Stable igg4 antibodies |
| EP2235064B1 (en) | 2008-01-07 | 2015-11-25 | Amgen Inc. | Method for making antibody fc-heterodimeric molecules using electrostatic steering effects |
| DE102008048942B4 (de) | 2008-09-25 | 2011-01-13 | Siemens Aktiengesellschaft | Anordnung mit einer Wellendichtung |
| US9493578B2 (en) * | 2009-09-02 | 2016-11-15 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
| RU2573915C2 (ru) * | 2009-09-16 | 2016-01-27 | Дженентек, Инк. | Содержащие суперспираль и/или привязку белковые комплексы и их применение |
| WO2011074717A1 (ko) | 2009-12-15 | 2011-06-23 | Choe Muhyeon | 단량체에 접착특이성이 있는 접착체의 반복사슬과 다수단량체의 복합체 내에서의 결합 가교의 생성 증가를 통한 이량체 및 다량체의 생산방법 |
| PT3272764T (pt) | 2009-12-18 | 2024-04-24 | Novartis Ag | Método para cromatografia de afinidade |
| CN103097417B (zh) * | 2010-04-20 | 2019-04-09 | 根马布股份公司 | 含异二聚体抗体fc的蛋白及其制备方法 |
| MX2012012321A (es) | 2010-04-22 | 2013-04-11 | Senesco Technologies Inc | Algas transgenicas con mejor expresion de aceite. |
| EP2560683B2 (en) | 2010-04-23 | 2022-07-20 | F. Hoffmann-La Roche AG | Production of heteromultimeric proteins |
| JP6022444B2 (ja) * | 2010-05-14 | 2016-11-09 | ライナット ニューロサイエンス コーポレイション | ヘテロ二量体タンパク質ならびにそれを生産および精製するための方法 |
| CA2850818A1 (en) * | 2011-10-11 | 2013-04-18 | Genentech, Inc. | Improved assembly of bispecific antibodies |
-
2012
- 2012-10-11 CA CA2850818A patent/CA2850818A1/en active Pending
- 2012-10-11 ES ES18167907T patent/ES2971444T3/es active Active
- 2012-10-11 KR KR1020207011816A patent/KR102219217B1/ko active IP Right Grant
- 2012-10-11 EP EP12778018.7A patent/EP2766397B1/en active Active
- 2012-10-11 HU HUE18167907A patent/HUE065876T2/hu unknown
- 2012-10-11 HR HRP20240230TT patent/HRP20240230T1/hr unknown
- 2012-10-11 EP EP18167907.7A patent/EP3418306B1/en active Active
- 2012-10-11 RU RU2014118743A patent/RU2654567C2/ru active
- 2012-10-11 MX MX2014004322A patent/MX359384B/es active IP Right Grant
- 2012-10-11 CN CN201280060881.5A patent/CN104093744A/zh active Pending
- 2012-10-11 CN CN201710312266.3A patent/CN107266577B/zh active Active
- 2012-10-11 PL PL12778018T patent/PL2766397T3/pl unknown
- 2012-10-11 TR TR2018/09151T patent/TR201809151T4/tr unknown
- 2012-10-11 KR KR1020147012233A patent/KR102106002B1/ko active Application Filing
- 2012-10-11 BR BR112014008684-2A patent/BR112014008684B1/pt active IP Right Grant
- 2012-10-11 ES ES12778018.7T patent/ES2682081T3/es active Active
- 2012-10-11 KR KR1020217004673A patent/KR102492792B1/ko active IP Right Grant
- 2012-10-11 PL PL18167907.7T patent/PL3418306T3/pl unknown
- 2012-10-11 WO PCT/US2012/059810 patent/WO2013055958A1/en active Application Filing
- 2012-10-11 JP JP2014535885A patent/JP6216321B2/ja active Active
- 2012-10-11 SI SI201231347T patent/SI2766397T1/sl unknown
-
2014
- 2014-04-11 US US14/251,428 patent/US9862778B2/en active Active
-
2015
- 2015-02-04 HK HK15101182.9A patent/HK1200844A1/xx unknown
- 2015-04-01 HK HK15103323.5A patent/HK1202878A1/xx unknown
-
2017
- 2017-10-20 US US15/789,775 patent/US10626189B2/en active Active
-
2018
- 2018-07-24 HR HRP20181189TT patent/HRP20181189T1/hr unknown
-
2020
- 2020-03-16 US US16/820,660 patent/US11725065B2/en active Active
-
2023
- 2023-06-15 US US18/210,604 patent/US20240101714A1/en active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11725065B2 (en) | Assembly of bispecific antibodies | |
| TWI798179B (zh) | 多特異性抗體之純化 | |
| JP6161540B2 (ja) | Ｆｃ変異体及びそれらの生産方法 | |
| KR101860963B1 (ko) | 이종다량체 단백질의 생산 | |
| JP6715186B2 (ja) | 哺乳動物細胞を用いたヘテロ多量体タンパク質の生成 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20151013 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20151013 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20161011 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20170106 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20170303 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170411 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20170829 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20170922 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6216321 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |